You searched for subject:(Messenger RNA)
.
Showing records 1 – 30 of
437 total matches.
◁ [1] [2] [3] [4] [5] … [15] ▶

Hong Kong University of Science and Technology
1.
Sun, Xin LIFS.
Identification of LDB3 as a PICK1 binding partner.
Degree: 2017, Hong Kong University of Science and Technology
URL: http://repository.ust.hk/ir/Record/1783.1-103556
;
https://doi.org/10.14711/thesis-991012564268803412
;
http://repository.ust.hk/ir/bitstream/1783.1-103556/1/th_redirect.html
► Delivery of different proteins to proper locations is important for them to exert specific function. Thereby, protein trafficking plays a critical role in maintaining the…
(more)
▼ Delivery of different proteins to proper locations is important for them to exert specific function. Thereby, protein trafficking plays a critical role in maintaining the normal cellular morphology and function. This complicated process involves hundreds of signaling molecules and proteins. PICK1 (Protein interacting with C-kinase 1) is a peripheral membrane protein expressed widely in various tissues. As the only protein containing both a PDZ domain and a BAR domain, PICK1 mainly functions in protein transport. In pancreas, PICK1 interacts with ICA69 (Islet cell autoantigen 69kDa) to form a complex responsible for the biogenesis and maturation of insulin granules. In pituitary gland, these two proteins bind together as well and regulate the storage and secretion of growth hormone. PICK1 is also involved in the formation of proacrosomal granules in testis and related to male infertility. However, currently only a few proteins have been identified as the binding partner of PICK1 responsible for protein trafficking and further investigation is required to fully elucidate the function of PICK1. In this study, LDB3 (LIM Domain Binding 3) was identified as a new PICK1 interacting protein by IP-MS method. These two proteins could bind to each other in vitro. Their interaction was further confirmed by in vivo co-immunoprecipitation experiment. Results of domain mapping assays showed that this interaction was dependent on the PDZ domain of PICK1 and the PDZ-binding motif at the C terminus of LDB3. Overexpressed in HEK293T cells, PICK1 and LDB3 co-localized together and formed unique vesicle-like structures. Moreover, these vesicle-like structures relied on their molecular interaction. Mutations abolishing the interaction of LDB3 and PICK1 totally disrupted their co-localization. Our data demonstrated that LDB3 could interact with PICK1 endogenously and their association might function in protein trafficking.
Subjects/Keywords: Proteins
; Messenger RNA
; Membrane proteins
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sun, X. L. (2017). Identification of LDB3 as a PICK1 binding partner. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-103556 ; https://doi.org/10.14711/thesis-991012564268803412 ; http://repository.ust.hk/ir/bitstream/1783.1-103556/1/th_redirect.html
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Sun, Xin LIFS. “Identification of LDB3 as a PICK1 binding partner.” 2017. Thesis, Hong Kong University of Science and Technology. Accessed February 27, 2021.
http://repository.ust.hk/ir/Record/1783.1-103556 ; https://doi.org/10.14711/thesis-991012564268803412 ; http://repository.ust.hk/ir/bitstream/1783.1-103556/1/th_redirect.html.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Sun, Xin LIFS. “Identification of LDB3 as a PICK1 binding partner.” 2017. Web. 27 Feb 2021.
Vancouver:
Sun XL. Identification of LDB3 as a PICK1 binding partner. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2017. [cited 2021 Feb 27].
Available from: http://repository.ust.hk/ir/Record/1783.1-103556 ; https://doi.org/10.14711/thesis-991012564268803412 ; http://repository.ust.hk/ir/bitstream/1783.1-103556/1/th_redirect.html.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Sun XL. Identification of LDB3 as a PICK1 binding partner. [Thesis]. Hong Kong University of Science and Technology; 2017. Available from: http://repository.ust.hk/ir/Record/1783.1-103556 ; https://doi.org/10.14711/thesis-991012564268803412 ; http://repository.ust.hk/ir/bitstream/1783.1-103556/1/th_redirect.html
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Lethbridge
2.
University of Lethbridge. Faculty of Arts and Science.
Elucidating the role of eukaryotic initiation factor 5B (eIF5B) in non-canonical translation initiation
.
Degree: 2019, University of Lethbridge
URL: http://hdl.handle.net/10133/5666
► Cap-dependent translation drives the global synthesis of proteins. Under stress conditions global protein production is attenuated, yet the translation of ATF4 is upregulated through uORF-…
(more)
▼ Cap-dependent translation drives the global synthesis of proteins. Under stress conditions global protein production is attenuated, yet the translation of ATF4 is upregulated through uORF- mediated translation initiation. eIF5B has been shown to deliver initiator-tRNA during non-canonical translation initiation. As such, we defined the role of eIF5B in the non-canonical translation of ATF4, and p27. Through polysome profiling and luciferase reporter assays, we confirmed that eIF5B facilitates uORF2-mediated repression of ATF4 translation. We determined that eIF5B has transcriptome-wide effects on signaling pathways, verifying activation of the JNK arm of the MAPK pathway and upregulation of dyskerin. I investigated the role eIF5B has in regulation of p27, and suggest that the mechanism is IRES-dependent. This study furthers the understanding into mechanisms of alternative translation initiation, which is critical to gene expression regulation.
Subjects/Keywords: Messenger RNA;
Proteins – Synthesis;
Ribosomes
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Science, U. o. L. F. o. A. a. (2019). Elucidating the role of eukaryotic initiation factor 5B (eIF5B) in non-canonical translation initiation
. (Thesis). University of Lethbridge. Retrieved from http://hdl.handle.net/10133/5666
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Science, University of Lethbridge. Faculty of Arts and. “Elucidating the role of eukaryotic initiation factor 5B (eIF5B) in non-canonical translation initiation
.” 2019. Thesis, University of Lethbridge. Accessed February 27, 2021.
http://hdl.handle.net/10133/5666.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Science, University of Lethbridge. Faculty of Arts and. “Elucidating the role of eukaryotic initiation factor 5B (eIF5B) in non-canonical translation initiation
.” 2019. Web. 27 Feb 2021.
Vancouver:
Science UoLFoAa. Elucidating the role of eukaryotic initiation factor 5B (eIF5B) in non-canonical translation initiation
. [Internet] [Thesis]. University of Lethbridge; 2019. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/10133/5666.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Science UoLFoAa. Elucidating the role of eukaryotic initiation factor 5B (eIF5B) in non-canonical translation initiation
. [Thesis]. University of Lethbridge; 2019. Available from: http://hdl.handle.net/10133/5666
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Hong Kong
3.
Lui, Wan, Thomas.
An analysis of the
functional significance of the 3'-untranslated region of
CHOP/Gadd153 messenger RNA.
Degree: 2013, University of Hong Kong
URL: http://hdl.handle.net/10722/192840
► CHOP, or Gadd153, is a 29 kDa protein that plays a pivotal role in the mediation of cellular stress-induced cell death. The expression of the…
(more)
▼ CHOP, or Gadd153, is a 29 kDa protein that
plays a pivotal role in the mediation of cellular stress-induced
cell death. The expression of the gene encoding CHOP/Gadd153 is
regulated at both the transcriptional and post-transcriptional
levels. Compared to transcription, the regulation of Chop gene
expression at the post-transcriptional level is much less
understood. In this study, the role played by the 3’-untranslated
region of CHOP mRNA (3UTRChop) in mediating mRNA stability was
examined. A reporter plasmid was constructed so that the mRNA
expressed has 3UTRChop as its 3’-untranslated region. Partial 5’
deletions, or deletion of short internal (~30 nucleotides)
sequences, or the deletion of a putative AU-rich element (ARE)
within 3UTRChop, all resulted in the elevation of the steady state
levels of mRNA and the encoded reporter protein, EGFP. Deletion of
the ARE or sequences remote from ARE resulted in the reduced rate
of mRNA degradation. Such data suggested that 3UTRChop is closely
related to mRNA stability.
The effect of cellular stress on the
functioning of 3UTRChop was studied by examining the change in mRNA
level in cells treated with arsenic trioxide (ATO). The presence of
arsenic stress stimulated a marked increase in the steady state
level of not only the reporter mRNA, but also control mRNAs that
did not have 3UTRChop as the 3’-untranslated region. A non-specific
effect of arsenic stress on mRNA levels was therefore suggested.
Consistent with the increase in the level of reporter mRNA, the
expression of EGFP protein was also increased. Arsenic stress and
partial deletion of 3UTRChop produce additive increase in mRNA
level and EGFP protein level implying that the mRNA destabilizing
function of 3UTRChop is unlikely to be stress-regulated.
The
contribution of 3UTRChop in mRNA translation was then examined
using reporter constructs that expressed EGFP mRNA having its
original 5’ and 3’-untranslated regions replaced with 5UTRChop and
3UTRChop respectively. In the presence of wild-type 3UTRChop, the
abolition of the translation repressor functions of 5UTRChop
produced only mild increase in EGFP expression. However, the
additional partial deletion of 3UTRChop resulted in massive
increase in EGFP expression. In the presence of wild-type 5UTRChop,
the partial deletion of 3UTRChop resulted in only a small increase
in EGFP expression. Such data demonstrated a complementary
relationship between 5UTRChop and 3UTRChop in the regulation of
Chop expression in unstressed cells. EGFP mRNA having 5UTRChop and
3UTRChop as the 5’ and 3’-untranslated region respectively
expressed significant EGFP protein only in the presence of ATO. The
expression of EGFP was not significantly affected with swopping of
3UTRChop with another 3UTR. 3UTRChop is therefore not essential for
the mediation of ATO-stimulated expression of EGFP.
The present
study demonstrated that full length 3UTRChop may have constitutive
mRNA destabilizing effect that is not alleviated by cellular
stress. The evaluation of the relative contributions of…
Advisors/Committee Members: Wong, NS (advisor).
Subjects/Keywords: Messenger RNA.
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lui, Wan, T. (2013). An analysis of the
functional significance of the 3'-untranslated region of
CHOP/Gadd153 messenger RNA. (Thesis). University of Hong Kong. Retrieved from http://hdl.handle.net/10722/192840
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Lui, Wan, Thomas. “An analysis of the
functional significance of the 3'-untranslated region of
CHOP/Gadd153 messenger RNA.” 2013. Thesis, University of Hong Kong. Accessed February 27, 2021.
http://hdl.handle.net/10722/192840.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lui, Wan, Thomas. “An analysis of the
functional significance of the 3'-untranslated region of
CHOP/Gadd153 messenger RNA.” 2013. Web. 27 Feb 2021.
Vancouver:
Lui, Wan T. An analysis of the
functional significance of the 3'-untranslated region of
CHOP/Gadd153 messenger RNA. [Internet] [Thesis]. University of Hong Kong; 2013. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/10722/192840.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Lui, Wan T. An analysis of the
functional significance of the 3'-untranslated region of
CHOP/Gadd153 messenger RNA. [Thesis]. University of Hong Kong; 2013. Available from: http://hdl.handle.net/10722/192840
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Missouri – Columbia
4.
Shebl, Bassem.
The influence of mRNA secondary structures on ribosome conformational dynamics.
Degree: 2016, University of Missouri – Columbia
URL: http://hdl.handle.net/10355/62520
► [ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Synthesizing proteins in the cell is a critical aspect of life. Protein synthesis is a…
(more)
▼ [ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Synthesizing proteins in the cell is a critical aspect of life. Protein synthesis is a complicated process and involve highly functional machines at a molecular level. The ribosome is the molecular machine that translate coded sequences of nucleic acids into functional proteins. Understanding how ribosomes function is key to understanding protein synthesis / translation. We focus our work on ribosomes from bacterial cells. This allows us to study much simpler systems and extrapolate our knowledge to higher levels. One key challenge in the field is to be able to isolate a high quantity of good and active ribosomes out of the cell to study it in a controlled environment. Classically known methods involve extensive resources, high technical expertise, and a week of preparation. We developed a one-step protocol to purify ribosomes that are more active than the ones purified from classical methods. This developed technique saves time and money and results in much higher amounts of product. This approach also makes the technique approachable to a wider community of scientists and researchers. The same methodology could be applied towards purifying other molecular machines in the cells. Using these ribosomes, we wanted to investigate how the ribosomes function in cells when faced with specific signals. These signals are utilized by the cells to control protein synthesis. However, in dome diseased cells and for some viruses, normal protein synthesis is overridden by the invaders to produce faulty proteins that could result in a wide range of diseases such as Alzheimer and others. In this study, we investigated how the ribosome functions in the presence of such signals and how close do they need to be to the ribosome to affect protein synthesis. This allows us to design drugs to mimic or inhibit such changes thus fixing faulty protein production or sometimes induce it to inhibit protein synthesis in bacterial cells and as such designing and producing novel drugs.
Advisors/Committee Members: Cornish, Peter V. (advisor).
Subjects/Keywords: Proteins – Synthesis; Messenger RNA; Ribosomes
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Shebl, B. (2016). The influence of mRNA secondary structures on ribosome conformational dynamics. (Thesis). University of Missouri – Columbia. Retrieved from http://hdl.handle.net/10355/62520
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Shebl, Bassem. “The influence of mRNA secondary structures on ribosome conformational dynamics.” 2016. Thesis, University of Missouri – Columbia. Accessed February 27, 2021.
http://hdl.handle.net/10355/62520.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Shebl, Bassem. “The influence of mRNA secondary structures on ribosome conformational dynamics.” 2016. Web. 27 Feb 2021.
Vancouver:
Shebl B. The influence of mRNA secondary structures on ribosome conformational dynamics. [Internet] [Thesis]. University of Missouri – Columbia; 2016. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/10355/62520.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Shebl B. The influence of mRNA secondary structures on ribosome conformational dynamics. [Thesis]. University of Missouri – Columbia; 2016. Available from: http://hdl.handle.net/10355/62520
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Rutgers University
5.
Zhou, Mi, 1987-.
Role of DcpS in mammalian RNA regulation and human diseases.
Degree: PhD, Cell and Developmental Biology, 2015, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/48745/
► In eukaryotic cells, mRNA degradation plays an important role in the control of gene expression and is therefore highly regulated. The scavenger decapping enzyme DcpS…
(more)
▼ In eukaryotic cells, mRNA degradation plays an important role in the control of gene expression and is therefore highly regulated. The scavenger decapping enzyme DcpS is a multifunctional protein that plays a critical role in mRNA degradation. We first sought to identify DcpS target genes in mammalian cells using a cell permeable DcpS inhibitor compound, RG3039, which was initially developed for therapeutic treatment of Spinal Muscular Atrophy (SMA). Microarray analysis following DcpS decapping inhibition by RG3039 revealed the steady state levels of 222 RNAs were altered. Of a subset selected for validation by qRT-PCR, two non-coding transcripts dependent on DcpS decapping activity, were identified and referred to as DcpS Responsive Noncoding Transcript (DRNT) 1 and 2 respectively. Only the increase in DRNT1 transcript was accompanied with an increase of its RNA stability and this increase was dependent on both DcpS and Xrn1. Our data indicate that DcpS is a transcript-restricted modulator of RNA stability in mammalian cells and the RG3039 quinazoline compound is pleotropic, influence gene expression in both an apparent DcpS dependent and independent manner. A surprising development was uncovered in a collaborative study where two distinct mutations in the DcpS gene (c.636+1G>A, DcpSIns15 and c.947C>T, DcpST316M) were identified as the underlying cause of autosomal recessive intellectual disability within a consanguineous family. Both of the mutations were confirmed to disrupt DcpS decapping activity in vitro and/or in vivo, indicating that the decapping activity of DcpS is critical for normal neurological development. Consistent with a role for DcpS in neuronal cells, our studies with the DcpSIns15 variant uncovered a link between this variant DcpS and Spinal Muscular Atrophy (SMA). Exogenous expression of DcpSIns15 in SMA patient fibroblast cells increased SMN2 mRNA and corresponding SMN protein levels. Our findings suggest that strategies to shift wild type DcpS splicing patterns to partially yield the variant DcpS Ins15 splicing pattern may be beneficial for SMA therapeutics.
Advisors/Committee Members: Kiledjian, Megerditch (chair), Covey, Lori (internal member), Gunderson, Samuel (internal member), Copeland, Paul (outside member).
Subjects/Keywords: Messenger RNA; Gene expression
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zhou, Mi, 1. (2015). Role of DcpS in mammalian RNA regulation and human diseases. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/48745/
Chicago Manual of Style (16th Edition):
Zhou, Mi, 1987-. “Role of DcpS in mammalian RNA regulation and human diseases.” 2015. Doctoral Dissertation, Rutgers University. Accessed February 27, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/48745/.
MLA Handbook (7th Edition):
Zhou, Mi, 1987-. “Role of DcpS in mammalian RNA regulation and human diseases.” 2015. Web. 27 Feb 2021.
Vancouver:
Zhou, Mi 1. Role of DcpS in mammalian RNA regulation and human diseases. [Internet] [Doctoral dissertation]. Rutgers University; 2015. [cited 2021 Feb 27].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/48745/.
Council of Science Editors:
Zhou, Mi 1. Role of DcpS in mammalian RNA regulation and human diseases. [Doctoral Dissertation]. Rutgers University; 2015. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/48745/

University of Minnesota
6.
Nair, Asha.
A novel bioinformatics approach to characterize and integrate messenger RNAs, circular RNAs and micro RNAs.
Degree: PhD, Biomedical Informatics and Computational Biology, 2018, University of Minnesota
URL: http://hdl.handle.net/11299/199034
► High-throughput Next Generation RNA sequencing (RNA-Seq) technology is affluent with information about the transcriptome, which includes both protein-coding and multiple non-coding regions. In a diseased…
(more)
▼ High-throughput Next Generation RNA sequencing (RNA-Seq) technology is affluent with information about the transcriptome, which includes both protein-coding and multiple non-coding regions. In a diseased state, complex interactions between these regions can go awry. Identification of such interactions is critical to translate the underlying biology of the transcriptome, especially for lethal diseases such as cancer. The field of bioinformatics is currently deficient in workflows that can analyze both coding and non-coding regions together efficiently, to identify disease-specific interactions. In this dissertation, I developed three coherent bioinformatics solutions that aim to address these shortcomings in RNA-Seq. First, a comprehensive workflow called MAPR-Seq was developed to analyze and report various features of protein-coding messenger RNAs. Second, a workflow for non-coding circular RNAs, called Circ-Seq, was developed to identify, quantify and annotate expressed circular RNAs. Third, an integration workflow called ReMIx was developed to identify microRNA response elements (MREs) and integrate them with the different types of RNAs (messenger RNAs, circular RNAs, and microRNAs). Collectively, the three workflows were applied to the largest cohort of breast cancer samples (n=885) from The Cancer Genome Atlas (TCGA). Based on the results obtained from these workflows, I present several key findings that are pertinent to breast cancer. I show that circular RNAs may be a marker for tumor proliferation in estrogen response positive (ER+) breast cancer subtype. I also show how triple negative (TN) breast cancer subtype-specific MRE signatures of messenger RNA – microRNA interactions can be obtained using RNA-Seq data, which has not been explored to date and thus, is a novel undertaking. In the end, my results highlight candidate messenger RNAs, circular RNAs and microRNAs that are found to be associated with MAPK and PI3K/AKT signaling cascades in TN breast cancer subtype. In general, the developed bioinformatics solutions can also be applied to RNA-Seq data of other cancer subtypes and diseases to identify unique messenger RNA – microRNA – circular RNA candidates that could be promising diagnostic targets towards improving treatment options for complex diseases.
Subjects/Keywords: circular RNA; integration; messenger RNA; micro RNA; MRE; RNA-Seq
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Nair, A. (2018). A novel bioinformatics approach to characterize and integrate messenger RNAs, circular RNAs and micro RNAs. (Doctoral Dissertation). University of Minnesota. Retrieved from http://hdl.handle.net/11299/199034
Chicago Manual of Style (16th Edition):
Nair, Asha. “A novel bioinformatics approach to characterize and integrate messenger RNAs, circular RNAs and micro RNAs.” 2018. Doctoral Dissertation, University of Minnesota. Accessed February 27, 2021.
http://hdl.handle.net/11299/199034.
MLA Handbook (7th Edition):
Nair, Asha. “A novel bioinformatics approach to characterize and integrate messenger RNAs, circular RNAs and micro RNAs.” 2018. Web. 27 Feb 2021.
Vancouver:
Nair A. A novel bioinformatics approach to characterize and integrate messenger RNAs, circular RNAs and micro RNAs. [Internet] [Doctoral dissertation]. University of Minnesota; 2018. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/11299/199034.
Council of Science Editors:
Nair A. A novel bioinformatics approach to characterize and integrate messenger RNAs, circular RNAs and micro RNAs. [Doctoral Dissertation]. University of Minnesota; 2018. Available from: http://hdl.handle.net/11299/199034

University of Utah
7.
Ball, Jennifer R.
RNA recognition by the nucleoporin Nup153;.
Degree: PhD, Oncological Sciences;, 2004, University of Utah
URL: http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/11/rec/1150
► Trafficking events across the nuclear envelope (NE) require specific interactions between cargo-receptor complexes and proteins of the nuclear pore complex (NPC). Although great strides have…
(more)
▼ Trafficking events across the nuclear envelope (NE) require specific interactions between cargo-receptor complexes and proteins of the nuclear pore complex (NPC). Although great strides have been made to elucidate protein and RNA transport pathways, many aspects of nuclear transport, particularly how cargo interacts with components of the NPC, remain undefined. In order to better understand the interactions that drive RNA export, I have focused on further defining the association between RNA cargo and the nucleoporin Nup153, a central regulator of nuclear transport. Overexpression of a C-terminal fragment of Nup153 in somatic cells inhibited poly(A)+ RNA export suggesting that Nup153 contributes to mRNA export. Further, perturbation of Nup153 function in Xenopus oocytes demonstrated Nup153 is important for mRNA, U snRNA and 5S rRNA export. Moreover, an RNA binding domain was mapped within the N-terminus of Nup 153 and was shown to bind RNA directly. The property of RNA association is conserved in Drosophila, Xenopus and human, underscoring the importance of this domain in higher eukaryotes. Although it is clear that Nup153 function is important for RNA export, exactly how this nuclear pore protein contributes to RNA export is unknown. One way to elucidate how Nup153 interfaces with RNA in the cell is to dissect the interactions mediated by this nucleoporin. Towards this end, the goal of this dissertation is to define the molecular targets of Nup153 in order to better understand the mechanisms by which Nup153, and the pore itself, functions. Initially, I found that the RNA binding domain (RBD) of Nup153 associates with cellular RNA and further characterization of this domain revealed that Nup153 preferentially associates with single-stranded RNA in a manner that distinctly mirrors properties that relay the identity of mRNA to the nuclear export machinery. I have also defined minimal length and base composition requirements for RNA association with Nup153. In collaboration with others, I have correlated Nup153-RNA association with functional RNA export in vivo. These collaborative studies indicate that direct contact between mRNA and Nup153 may occur cooperatively with protein contacts and that this interface between Nup153, mRNA and protein is critical to mRNA export and potentially concurrent mRNP remodeling and quality control.
Subjects/Keywords: Physiology; RNA Messenger
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ball, J. R. (2004). RNA recognition by the nucleoporin Nup153;. (Doctoral Dissertation). University of Utah. Retrieved from http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/11/rec/1150
Chicago Manual of Style (16th Edition):
Ball, Jennifer R. “RNA recognition by the nucleoporin Nup153;.” 2004. Doctoral Dissertation, University of Utah. Accessed February 27, 2021.
http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/11/rec/1150.
MLA Handbook (7th Edition):
Ball, Jennifer R. “RNA recognition by the nucleoporin Nup153;.” 2004. Web. 27 Feb 2021.
Vancouver:
Ball JR. RNA recognition by the nucleoporin Nup153;. [Internet] [Doctoral dissertation]. University of Utah; 2004. [cited 2021 Feb 27].
Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/11/rec/1150.
Council of Science Editors:
Ball JR. RNA recognition by the nucleoporin Nup153;. [Doctoral Dissertation]. University of Utah; 2004. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/11/rec/1150

University of Texas Southwestern Medical Center
8.
Tsai, Pei-Ling.
The Role of NS1-BP in Influenza Virus Replication.
Degree: 2012, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/1100
► Influenza A viruses are negative-sense, segmented RNA viruses which cause about 500,000 deaths worldwide per year. Genomic studies have shown that the non-structural protein (NS1)…
(more)
▼ Influenza A viruses are negative-sense, segmented
RNA viruses which cause about 500,000 deaths worldwide per year. Genomic studies have shown that the non-structural protein (NS1) of influenza A virus is a major virulence factor that is essential for pathogenesis. NS1 is a multifunctional protein localized in the nucleus and in the cytoplasm. In the cytoplasm, NS1 inhibits host signaling pathways that result in down-regulation of interferon expression and innate immune response. In the nucleus, NS1 represses host gene expression. I have shown that NS1 binds an mRNA complex containing NXF1/TAP, NXT/p15, Rae1, and E1B-AP5, which are key components of the mRNA export machinery. By targeting this complex, NS1 blocks host mRNA export, and cells become highly permissive to viral replication. Another intranuclear pool of NS1 was found to interact with a host protein termed NS1-BP, which has been suggested to play a role in pre-mRNA splicing. However, the functions and mechanisms of NS1-BP involved in influenza life cycle remain to be elucidated. To investigate the function of NS1-BP, I first identified its binding partners by immunoprecipitation followed by mass spectrometry. I found interactions of NS1-BP with viral polymerase complex and host
RNA polymerase II indicating that NS1-BP has a role in regulating viral
RNA transcription and replication. I further showed that low levels of NS1-BP led to a decrease in viral polymerase activity resulting in inhibition of virus replication. Thus, I identified NS1-BP as a novel pro-viral factor required for proper replication of influenza virus. Since NS1 is a key contributor to the virulence of influenza viruses, discovering the function of NS1 interacting partners has major implications for antiviral therapy.
Advisors/Committee Members: Fontoura, Beatriz.
Subjects/Keywords: Nuclear Pore; Influenza A Virus; RNA, Messenger
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Tsai, P. (2012). The Role of NS1-BP in Influenza Virus Replication. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/1100
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Tsai, Pei-Ling. “The Role of NS1-BP in Influenza Virus Replication.” 2012. Thesis, University of Texas Southwestern Medical Center. Accessed February 27, 2021.
http://hdl.handle.net/2152.5/1100.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Tsai, Pei-Ling. “The Role of NS1-BP in Influenza Virus Replication.” 2012. Web. 27 Feb 2021.
Vancouver:
Tsai P. The Role of NS1-BP in Influenza Virus Replication. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2012. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/2152.5/1100.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Tsai P. The Role of NS1-BP in Influenza Virus Replication. [Thesis]. University of Texas Southwestern Medical Center; 2012. Available from: http://hdl.handle.net/2152.5/1100
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Texas Southwestern Medical Center
9.
Tuckerman, Jason Robert.
Heme-Based Oxygen Sensors of Commensal, Symbiotic, and Pathogenic Bacteria.
Degree: 2012, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/1115
► Direct oxygen sensors are proteins that serve as "on-off switches" to cause reversible and adaptive changes in the activities of other proteins or genes, with…
(more)
▼ Direct oxygen sensors are proteins that serve as "on-off switches" to cause reversible and adaptive changes in the activities of other proteins or genes, with great specificity in response to fluctuations in oxygen concentration. The heme-based oxygen sensors are a large class of direct oxygen sensors that feature direct binding of oxygen to a sensory heme-containing domain. This heme-binding region couples to a regulatory domain within the same polypeptide. The types of functionalities controlled by these oxygen-specific switches are diverse, and include the regulation of protein activities, gene expression, and second
messenger elaboration. A primary focus of this work was the biochemical characterization of a pair of heme-based oxygen sensors involved in the control of the bacterial second
messenger cyclic diguanylic acid (c-di-GMP) in Escherichia coli. We discovered that these enzymes, designated DosC and DosP, serve as a diguanylate cyclase and c-di-GMP phosphodiesterase pair that associate with components of the E. coli
RNA degradosome in vivo. Importantly, one member of these degradosomes, PNPase, is a direct, high-affinity target of c-di-GMP. These findings imply that specialized oxygen-sensing degradosomes exist in E. coli. In these oxygen-sensing degradosomes cellular oxygen levels regulate PNPase processing of specific
RNA transcripts via c-di-GMP.
A secondary focus of this work was the characterization of a novel two-component system in M. tuberculosis involved in the non-replicating persistent phase of this bacterium in a typical TB infection. Here, the activities of two heme-containing histidine kinases, DosT and DevS, were discovered to be inhibited specifically by oxygen. As DosT and DevS are the primary regulators of the dormancy survival regulator (DosR/DevR) transcription factor, these results contributed a molecular explanation for the numerous observations linking oxygen and DevR to the dormancy phenotype of M. tuberculosis seen both in vitro and in vivo.
Advisors/Committee Members: Gilles-Gonzalez, Marie-Alda.
Subjects/Keywords: Cyclic GMP; RNA; Second Messenger Systems
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Tuckerman, J. R. (2012). Heme-Based Oxygen Sensors of Commensal, Symbiotic, and Pathogenic Bacteria. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/1115
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Tuckerman, Jason Robert. “Heme-Based Oxygen Sensors of Commensal, Symbiotic, and Pathogenic Bacteria.” 2012. Thesis, University of Texas Southwestern Medical Center. Accessed February 27, 2021.
http://hdl.handle.net/2152.5/1115.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Tuckerman, Jason Robert. “Heme-Based Oxygen Sensors of Commensal, Symbiotic, and Pathogenic Bacteria.” 2012. Web. 27 Feb 2021.
Vancouver:
Tuckerman JR. Heme-Based Oxygen Sensors of Commensal, Symbiotic, and Pathogenic Bacteria. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2012. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/2152.5/1115.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Tuckerman JR. Heme-Based Oxygen Sensors of Commensal, Symbiotic, and Pathogenic Bacteria. [Thesis]. University of Texas Southwestern Medical Center; 2012. Available from: http://hdl.handle.net/2152.5/1115
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Columbia University
10.
Martinez, Jose Carlos.
Regulation of Neuronal mRNA Localization by Exclusion.
Degree: 2018, Columbia University
URL: https://doi.org/10.7916/D8F49125
► Intra-axonal protein synthesis is important for the proper wiring of the nervous system and can have restorative or pathogenic effects in response to nerve injury…
(more)
▼ Intra-axonal protein synthesis is important for the proper wiring of the nervous system and can have restorative or pathogenic effects in response to nerve injury and neurodegenerative stimuli. The set of axonally translated transcripts, the axonal translatome, is regulated through the control of mRNA localization, stability, and translation. Targeting the axonal translatome could result in the development of novel therapies for the treatment of neurological disorders. Yet, there are gaps in our understanding of the selective mechanism regulating the specific localization of mRNAs into axons. Currently, axonal localization of transcripts is understood to be controlled by the presence of sequence elements that direct axonal transport. In an attempt to identify novel localization motifs, I found that a well-known motif corresponding to the Pumilio Binding Element (PBE) is significantly depleted in axonally enriched mRNAs. Moreover, I found this element to be highly informative of axonal mRNA localization and translation across different neuronal types and developmental stages suggesting that it is a highly conserved regulatory motif. I found Pum2 neuronal expression and subcellular localization to be highly consistent with the way the PBE predicts mRNA regulation. I then demonstrated that interfering with Pum2 function results in increased axonal localization of PBE containing mRNAs. Finally, Pum2 downregulation was associated with gross defects in axonal outgrowth, branching, and regeneration. Altogether, this data suggests that Pum2 regulates axonal mRNA localization through an exclusion mechanism that is important during neuronal development.
Subjects/Keywords: Neurosciences; Cytology; Messenger RNA; Nervous system
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Martinez, J. C. (2018). Regulation of Neuronal mRNA Localization by Exclusion. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/D8F49125
Chicago Manual of Style (16th Edition):
Martinez, Jose Carlos. “Regulation of Neuronal mRNA Localization by Exclusion.” 2018. Doctoral Dissertation, Columbia University. Accessed February 27, 2021.
https://doi.org/10.7916/D8F49125.
MLA Handbook (7th Edition):
Martinez, Jose Carlos. “Regulation of Neuronal mRNA Localization by Exclusion.” 2018. Web. 27 Feb 2021.
Vancouver:
Martinez JC. Regulation of Neuronal mRNA Localization by Exclusion. [Internet] [Doctoral dissertation]. Columbia University; 2018. [cited 2021 Feb 27].
Available from: https://doi.org/10.7916/D8F49125.
Council of Science Editors:
Martinez JC. Regulation of Neuronal mRNA Localization by Exclusion. [Doctoral Dissertation]. Columbia University; 2018. Available from: https://doi.org/10.7916/D8F49125
11.
Roalofs, Scott F.
Gene activity analysis of Saccharomyces cerevisiae metallo-aminopeptidase gene deletion strains using DNA microarrays and verification with quantitative RT-PCR.
Degree: MS(M.S.), Applied Natural Science, 2018, Colorado State University – Pueblo
URL: http://hdl.handle.net/10217/187682
► Metallo-Aminopeptidase gene family 1 (M1AP) encode enzymes that cleave 1-3 amino acids from the N-terminus of a peptide. Previous studies involving M1AP inhibitors indicate that…
(more)
▼ Metallo-Aminopeptidase gene family 1 (M1AP) encode enzymes that cleave 1-3 amino acids from the N-terminus of a peptide. Previous studies involving M1AP inhibitors indicate that M1APs may be involved in the cell cycle and have been used in the treatment of cancers. In previous studies from this lab, yeast strains disrupted in the above enzymes show a G2/M phase delay. To investigate the effects of M1APs in the cell cycle, Saccharomyces cerevisiae strains were developed with gene mutations in the open reading frames YHR047c (AAP1'), and YKL157w (APE2). To understand the global changes to gene regulation due to M1AP mutations, a genome wide analysis of mRNA accumulation using microarrays was attempted using total RNA isolated from log phase wild type and mutant cells. cDNA probes were developed and used for competitive hybridization on microarrays. Our data showed that mRNA abundances in cell signaling and spindle/bud formation were affected. These results are consistent with a role of the aminopeptidases in the G2/M phase of the cell cycle. Differentially expressed mRNA abundances identified by microarrays were randomly verified by quantitative reverse-transcribed PCR (qRT-PCR). The identification of cell cycle genes in M1AP mutants may provide insights into the molecular events leading to the G2/M phase delay and further understanding of the cell cycle.
Subjects/Keywords: Saccharomyces cerevisiae; Aminopeptidases; DNA microarrays; Messenger RNA
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Roalofs, S. F. (2018). Gene activity analysis of Saccharomyces cerevisiae metallo-aminopeptidase gene deletion strains using DNA microarrays and verification with quantitative RT-PCR. (Masters Thesis). Colorado State University – Pueblo. Retrieved from http://hdl.handle.net/10217/187682
Chicago Manual of Style (16th Edition):
Roalofs, Scott F. “Gene activity analysis of Saccharomyces cerevisiae metallo-aminopeptidase gene deletion strains using DNA microarrays and verification with quantitative RT-PCR.” 2018. Masters Thesis, Colorado State University – Pueblo. Accessed February 27, 2021.
http://hdl.handle.net/10217/187682.
MLA Handbook (7th Edition):
Roalofs, Scott F. “Gene activity analysis of Saccharomyces cerevisiae metallo-aminopeptidase gene deletion strains using DNA microarrays and verification with quantitative RT-PCR.” 2018. Web. 27 Feb 2021.
Vancouver:
Roalofs SF. Gene activity analysis of Saccharomyces cerevisiae metallo-aminopeptidase gene deletion strains using DNA microarrays and verification with quantitative RT-PCR. [Internet] [Masters thesis]. Colorado State University – Pueblo; 2018. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/10217/187682.
Council of Science Editors:
Roalofs SF. Gene activity analysis of Saccharomyces cerevisiae metallo-aminopeptidase gene deletion strains using DNA microarrays and verification with quantitative RT-PCR. [Masters Thesis]. Colorado State University – Pueblo; 2018. Available from: http://hdl.handle.net/10217/187682

Hong Kong University of Science and Technology
12.
Lam, Sheung Wai LIFS.
Elucidating the role of Pabpn1 in mRNA alternative polyadenylation during satellite cell activation.
Degree: 2016, Hong Kong University of Science and Technology
URL: http://repository.ust.hk/ir/Record/1783.1-100400
;
https://doi.org/10.14711/thesis-b1626258
;
http://repository.ust.hk/ir/bitstream/1783.1-100400/1/th_redirect.html
► Satellite cells are muscle stem cells that are primarily quiescent in resting muscle. Upon injury, satellite cells will activate, proliferate, and differentiate to repair the…
(more)
▼ Satellite cells are muscle stem cells that are primarily quiescent in resting muscle. Upon injury, satellite cells will activate, proliferate, and differentiate to repair the damaged muscle. The quiescent state is a tightly regulated process. Dysregulation of the quiescent state will result in a depletion of the stem cell pool and impairment of muscle regeneration. Previously, our group has identified that the microRNA (miRNA) pathway is essential for the maintanence of satellite cell quiescence. As binding sites of miRNAs are on the 3’ UTR of mRNAs, the susceptibility of mRNA to miRNA regulation would depend on lengths of 3’ UTRs. Therefore, we hypothesized that alternative polyadenylation plays an important post-transcriptional regulation to maintain satellite cell quiescence. Alternative polyadenylation involves a number of proteins. In particular, poly(A) binding protein nuclear 1 (PABPN1) has been implicated as an important regulator of polyadenylation site selection. To better understand the role of PABPN1 in mRNA alternative polyadenylation, the expression level of PABPN1 in vivo in uninjured, regenerating and regenerated muscle was characterized. In addition, the expression level of PABPN1 during satellite cell activation on satellite cells associated muscle fibers ex vivo and during differentiation in primary myoblasts in vitro was investigated. We found that PABPN1 was highly expressed in regenerating muscle and activated satellite cells. Knockdown experiments were also performed on single fibers to investigate the effect of PABPN1 on satellite cell number and proliferation. The result of this project will shed lights on how alternative polyadenylation regulates muscle stem cell function.
Subjects/Keywords: Satellite cells
; Messenger RNA
; Gene expression
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lam, S. W. L. (2016). Elucidating the role of Pabpn1 in mRNA alternative polyadenylation during satellite cell activation. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-100400 ; https://doi.org/10.14711/thesis-b1626258 ; http://repository.ust.hk/ir/bitstream/1783.1-100400/1/th_redirect.html
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Lam, Sheung Wai LIFS. “Elucidating the role of Pabpn1 in mRNA alternative polyadenylation during satellite cell activation.” 2016. Thesis, Hong Kong University of Science and Technology. Accessed February 27, 2021.
http://repository.ust.hk/ir/Record/1783.1-100400 ; https://doi.org/10.14711/thesis-b1626258 ; http://repository.ust.hk/ir/bitstream/1783.1-100400/1/th_redirect.html.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lam, Sheung Wai LIFS. “Elucidating the role of Pabpn1 in mRNA alternative polyadenylation during satellite cell activation.” 2016. Web. 27 Feb 2021.
Vancouver:
Lam SWL. Elucidating the role of Pabpn1 in mRNA alternative polyadenylation during satellite cell activation. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2016. [cited 2021 Feb 27].
Available from: http://repository.ust.hk/ir/Record/1783.1-100400 ; https://doi.org/10.14711/thesis-b1626258 ; http://repository.ust.hk/ir/bitstream/1783.1-100400/1/th_redirect.html.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Lam SWL. Elucidating the role of Pabpn1 in mRNA alternative polyadenylation during satellite cell activation. [Thesis]. Hong Kong University of Science and Technology; 2016. Available from: http://repository.ust.hk/ir/Record/1783.1-100400 ; https://doi.org/10.14711/thesis-b1626258 ; http://repository.ust.hk/ir/bitstream/1783.1-100400/1/th_redirect.html
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Hong Kong University of Science and Technology
13.
Wong, Julie Hiu Tung.
Defining the role of ncbp-1 and ncbp-2 to regulate sensory ray identity in C. elegans.
Degree: 2012, Hong Kong University of Science and Technology
URL: http://repository.ust.hk/ir/Record/1783.1-7527
;
https://doi.org/10.14711/thesis-b1176678
;
http://repository.ust.hk/ir/bitstream/1783.1-7527/1/th_redirect.html
► Gene modulations in eukaryotes are very important for guiding the differentiation of cell types that are specialized to serve a particular function. Pre-messenger ribonucleic acid…
(more)
▼ Gene modulations in eukaryotes are very important for guiding the differentiation of cell types that are specialized to serve a particular function. Pre-messenger ribonucleic acid (mRNA)-splicing and microRNA processing, coupled with non-sense mediated decay are common strategies adopted to control gene expression. Cap-binding complexes, which have subunits ncbp-1 and ncbp-2, are implicated to be required in all of these events in plants to humans, which suggest that they play a conserved role in the determination of cell fate. Indeed, ncbp-1 and ncbp-2 have been found to determine the fate and identities of ray cells in Caenorhabditis elegans. I have demonstrated that by reducing the levels of either ncbp-1 or ncbp-2, this transforms the identity of ray 6 to that of ray 4, which results in rays 6-4 fusion. It has been confirmed that NCBP-1 and NCBP-2 co-localize at ray precursor cells and able to physically interact with each other via translational reporters and yeast-2-hybrid assays respectively. Therefore, it is suggested that they work together for ray patterning. In addition, ncbp-1/ncbp-2 is demonstrated to regulate ray identities by repressing Dbl/Sma signaling, rather than having a direct influence on the components of the pathway. ncbp-1/ncbp-2 is suggested to influence at the mRNA level, as it binds to the mRNA of dbl-1. This interaction is likely to be at the rays, and not at the ventral nerve cord. The findings of this study confirm the roles of ncbp-1 and ncbp-2 in cell fate determination, and inspire us on their possible mechanisms and targets.
Subjects/Keywords: Caenorhabditis elegans – Genetics
; Messenger RNA
; Protein binding
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wong, J. H. T. (2012). Defining the role of ncbp-1 and ncbp-2 to regulate sensory ray identity in C. elegans. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-7527 ; https://doi.org/10.14711/thesis-b1176678 ; http://repository.ust.hk/ir/bitstream/1783.1-7527/1/th_redirect.html
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Wong, Julie Hiu Tung. “Defining the role of ncbp-1 and ncbp-2 to regulate sensory ray identity in C. elegans.” 2012. Thesis, Hong Kong University of Science and Technology. Accessed February 27, 2021.
http://repository.ust.hk/ir/Record/1783.1-7527 ; https://doi.org/10.14711/thesis-b1176678 ; http://repository.ust.hk/ir/bitstream/1783.1-7527/1/th_redirect.html.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Wong, Julie Hiu Tung. “Defining the role of ncbp-1 and ncbp-2 to regulate sensory ray identity in C. elegans.” 2012. Web. 27 Feb 2021.
Vancouver:
Wong JHT. Defining the role of ncbp-1 and ncbp-2 to regulate sensory ray identity in C. elegans. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2012. [cited 2021 Feb 27].
Available from: http://repository.ust.hk/ir/Record/1783.1-7527 ; https://doi.org/10.14711/thesis-b1176678 ; http://repository.ust.hk/ir/bitstream/1783.1-7527/1/th_redirect.html.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Wong JHT. Defining the role of ncbp-1 and ncbp-2 to regulate sensory ray identity in C. elegans. [Thesis]. Hong Kong University of Science and Technology; 2012. Available from: http://repository.ust.hk/ir/Record/1783.1-7527 ; https://doi.org/10.14711/thesis-b1176678 ; http://repository.ust.hk/ir/bitstream/1783.1-7527/1/th_redirect.html
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

New Jersey Institute of Technology
14.
Nambiar, Ram Mohan.
PolyA DB3: a database cataloging polyadenation sites(pas) across different species and their conservation.
Degree: MSin Bioinformatics - (M.S.), Computer Science, 2018, New Jersey Institute of Technology
URL: https://digitalcommons.njit.edu/theses/1636
► Polyadenation is an important process occurring in the messenger RNA that involves cleavage of 3 end nascent mRNAs and addition of poly(A) tails. For…
(more)
▼ Polyadenation is an important process occurring in the
messenger RNA that involves cleavage of 3 end nascent mRNAs and addition of poly(A) tails. For this thesis,I present PolyA DB3 ,a database cataloging cleavage and polyadenylation sites (PASs) in several genomes specifically for human,mouse,rat and chicken. This database is based on deep sequencing data. PASs are mapped by the 3’ region extraction and deep sequencing (3’READS) method, ensuring unequivocal PAS identification. Large volume of data based on diverse biological samples is used to increase PAS coverage and provide PAS usage information. Strand-specific
RNA-seq data were used to extend annotated 3’ ends of genes to obtain more thorough annotations of alternative polyadenylation (APA) sites. The database also has information regarding conservation of PAS between these species. Similar analysis has also been done on the PASs identified from frog samples and the identification of conservation of the PASs.
Advisors/Committee Members: Bin Tian, Usman W. Roshan, Zhi Wei.
Subjects/Keywords: Polyadenation; Messenger RNA; Bioinformatics; Computer Sciences
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Nambiar, R. M. (2018). PolyA DB3: a database cataloging polyadenation sites(pas) across different species and their conservation. (Thesis). New Jersey Institute of Technology. Retrieved from https://digitalcommons.njit.edu/theses/1636
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Nambiar, Ram Mohan. “PolyA DB3: a database cataloging polyadenation sites(pas) across different species and their conservation.” 2018. Thesis, New Jersey Institute of Technology. Accessed February 27, 2021.
https://digitalcommons.njit.edu/theses/1636.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Nambiar, Ram Mohan. “PolyA DB3: a database cataloging polyadenation sites(pas) across different species and their conservation.” 2018. Web. 27 Feb 2021.
Vancouver:
Nambiar RM. PolyA DB3: a database cataloging polyadenation sites(pas) across different species and their conservation. [Internet] [Thesis]. New Jersey Institute of Technology; 2018. [cited 2021 Feb 27].
Available from: https://digitalcommons.njit.edu/theses/1636.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Nambiar RM. PolyA DB3: a database cataloging polyadenation sites(pas) across different species and their conservation. [Thesis]. New Jersey Institute of Technology; 2018. Available from: https://digitalcommons.njit.edu/theses/1636
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Hong Kong
15.
Wong, Po-yu.
The 3'-untranslated region
of CHOP mRNA encodes information that determines the expression
level of the CHOP gene.
Degree: 2015, University of Hong Kong
URL: http://hdl.handle.net/10722/223569
► CHOP is a stress-inducible protein that acts as a transcription co-regulatory factor for genes that are involved in cellular responses to stress. Previous studies demonstrated…
(more)
▼ CHOP is a stress-inducible protein that acts
as a transcription co-regulatory factor for genes that are involved
in cellular responses to stress. Previous studies demonstrated that
the activation of promoter activity of the CHOP gene is a major
mechanism underlying the increase in the mRNA level of the CHOP
gene in stressed cells. It is however not certain if the cellular
mRNA degradation mechanism for CHOP mRNA might also be
stress-sensitive so that together with stress-stimulated
transcription a highly precise control of CHOP mRNA level can be
achieved. To examine such a possibility, a series of
CHOP-expressing plasmids were constructed and used to express the
full length CHOP mRNA with or without deletion mutations in its
3’untranslated region in cultured cells. Realtime PCR quantitation
demonstrated that the level of the expressed full length CHOP mRNA
was the same in unstressed and stressed cells. Deletion mutations
of the 3UTR of CHOP mRNA resulted in changes of CHOP-mRNA levels
relative to the wild type mRNA but otherwise such changes were not
affected by cellular stress. To ascertain if deletion mutations of
the 3’UTR of CHOP mRNA alone were sufficient to cause changes in
mRNA levels without requiring the participation of the rest of the
CHOP mRNA sequence, another series of expression plasmids were
constructed that will express EGFP mRNA having its original 3’UTR
replaced with either the 3’UTR of CHOP mRNA, or 3’UTR of CHOP mRNA
with deletions mutations the same as those of the pCHOP series of
plasmids. Analysis of real-time PCR data obtained for the
quantitation of mRNA levels expressed from the E3 series of
plasmids showed the same changes of the expressed mRNA levels
caused by the deletion mutations in the 3’UTR. The changes in mRNA
levels were again independent of cellular stress. To examine if the
change in mRNA levels would result in proportionate changes of
translation, the abundance of the reporter protein (GFP) expressed
from plasmids of the E3-series was quantitated directly by Western
blot and indirectly by measurement of FITC fluorescence by FACS
analysis. The decrease in mRNA expression due to the deletion of
the first 30 ribonucleotides in the 3’UTR CHOP is always met with
more of less proportionate decrease in the reporter protein
expressed from this mutant mRNA. However, the change in mRNA level
expressed from other pCHOP and E3 deletion mutants may not always
cause a corresponding change in level of translational product.
Results of this study suggest that unlike transcriptional synthesis
of CHOP mRNA that is tightly stress-regulated, the degradation
mechanism of CHOP mRNA is stress-insensitive and it may only be
passively involved in preventing excessive synthesis of the CHOP
mRNA. The degradation of the CHOP is closely related to the
nucleotide sequence of its 3’UTR. Additional function of the
nucleotide sequence of the 3’UTR of CHOP mRNA is also suggested by
results of the present study.
Subjects/Keywords: Messenger RNA;
Cytogenetics
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wong, P. (2015). The 3'-untranslated region
of CHOP mRNA encodes information that determines the expression
level of the CHOP gene. (Thesis). University of Hong Kong. Retrieved from http://hdl.handle.net/10722/223569
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Wong, Po-yu. “The 3'-untranslated region
of CHOP mRNA encodes information that determines the expression
level of the CHOP gene.” 2015. Thesis, University of Hong Kong. Accessed February 27, 2021.
http://hdl.handle.net/10722/223569.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Wong, Po-yu. “The 3'-untranslated region
of CHOP mRNA encodes information that determines the expression
level of the CHOP gene.” 2015. Web. 27 Feb 2021.
Vancouver:
Wong P. The 3'-untranslated region
of CHOP mRNA encodes information that determines the expression
level of the CHOP gene. [Internet] [Thesis]. University of Hong Kong; 2015. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/10722/223569.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Wong P. The 3'-untranslated region
of CHOP mRNA encodes information that determines the expression
level of the CHOP gene. [Thesis]. University of Hong Kong; 2015. Available from: http://hdl.handle.net/10722/223569
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Texas – Austin
16.
Zicker, Alicia A.
Distinct roles for the 5' and 3' untranslated regions in the degradation and stability of chloroplast tufA mRNA.
Degree: PhD, Ecology, Evolution, and Behavior, 2005, University of Texas – Austin
URL: http://hdl.handle.net/2152/1765
► The tufA gene encodes the chloroplast elongation factor Tu and is found in the chloroplast genome in Chlamydomonas reinhardtii, whereas it is in the nucleus…
(more)
▼ The tufA gene encodes the chloroplast elongation factor Tu and is found in
the chloroplast genome in Chlamydomonas reinhardtii, whereas it is in the
nucleus in land plants. When C. reinhardtii is treated with chloramphenicol
(CAP), an inhibitor of ribosome elongation, the stability of the 1.7-kb tufA mRNA
is increased, and a
RNA of ~1.5 kb over-accumulates. When CAP and the
transcription inhibitor rifampicin are added together, tufA mRNA can be chased
into the 1.5-kb
RNA (which is subsequently degraded), suggesting that it is an
intermediate in the degradation pathway. Mapping of the 5' and 3' ends of the
1.5-kb
RNA showed that it is truncated at the 5' end, and is missing 177-181
nucleotides; there was no evidence of truncation at the 3' end. The 5' end of this
intermediate lies 76-80 nucleotides upstream of the tufA start codon, and within a
vii
small ORF that has predicted secondary structure. Interestingly, the degradation
intermediate did not over-accumulate in a chloroplast ribosome-deficient mutant,
suggesting that its stabilization requires elongation-arrested ribosomes. Finally,
evidence was obtained that the intermediate accumulates in the absence of CAP,
especially in older cultures. These results indicate that a major pathway for
degradation of tufA mRNA in vivo begins at the 5' end of the
RNA, probably with
an endonucleolytic cleavage, but 5' to 3' exonuclease activity cannot be ruled out.
To determine whether the 5' or 3' UTR of tufA is destabilizing, the
corresponding regions of an atpA-aadA-rbcL gene (which gives high mRNA
levels) were replaced with one or both tufA UTRs, and transformed into the
chloroplast. Northern blot analysis of the transformants indicated, quite
surprisingly, that the 3' UTR of tufA is strongly destabilizing. The results suggest
that the UTRs of tufA have distinct, but also interacting roles in mediating decay
of tufA mRNA.
To determine if the 3' UTR of tufA can regulate protein expression,
constructs were made using Renilla luciferase as reporter, and transformed into
chloroplasts. Luminescence measurements of the transformants indicated that the
3' UTR of tufA can regulate expression at the protein level, but no more so than
the 5' UTR
Advisors/Committee Members: Herrin, David L. (advisor).
Subjects/Keywords: Chloroplasts; Messenger RNA
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zicker, A. A. (2005). Distinct roles for the 5' and 3' untranslated regions in the degradation and stability of chloroplast tufA mRNA. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/1765
Chicago Manual of Style (16th Edition):
Zicker, Alicia A. “Distinct roles for the 5' and 3' untranslated regions in the degradation and stability of chloroplast tufA mRNA.” 2005. Doctoral Dissertation, University of Texas – Austin. Accessed February 27, 2021.
http://hdl.handle.net/2152/1765.
MLA Handbook (7th Edition):
Zicker, Alicia A. “Distinct roles for the 5' and 3' untranslated regions in the degradation and stability of chloroplast tufA mRNA.” 2005. Web. 27 Feb 2021.
Vancouver:
Zicker AA. Distinct roles for the 5' and 3' untranslated regions in the degradation and stability of chloroplast tufA mRNA. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2005. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/2152/1765.
Council of Science Editors:
Zicker AA. Distinct roles for the 5' and 3' untranslated regions in the degradation and stability of chloroplast tufA mRNA. [Doctoral Dissertation]. University of Texas – Austin; 2005. Available from: http://hdl.handle.net/2152/1765

Columbia University
17.
Hamilton, Keith.
Structural and Biochemical Studies of the Human pre-mRNA 3’-end Processing Complex.
Degree: 2021, Columbia University
URL: https://doi.org/10.7916/d8-6xaw-xv26
► Most eukaryotic pre-mRNAs undergo 3′-end cleavage and polyadenylation prior to their export from the nucleus. A large number of proteins in several complexes participate in…
(more)
▼ Most eukaryotic pre-mRNAs undergo 3′-end cleavage and polyadenylation prior to their export from the nucleus. A large number of proteins in several complexes participate in this 3′-end processing, including cleavage and polyadenylation specificity factor (CPSF) in mammals. The CPSF can be further divided into two sub-complexes: mPSF (mammalian polyadenylation specificity factor) which recognizes the AAUAAA polyadenylation signal (PAS) in the pre- mRNA, and mCF (mammalian cleavage factor) which cleaves the RNA. mPSF consists of CPSF160, CPSF30, WDR33, and hFip1. This thesis shows that AAUAAA PAS is recognized with ∼3 nM affinity by the CPSF160–WDR33–CPSF30 ternary complex, while the proteins alone or the binary complexes do not bind the PAS with high affinity. Furthermore, it is shown that mutations of residues in CPSF30 that have van der Waals interactions with the bases of the PAS lead to a sharp reduction in the affinity. Finally, variations of the AAUAAA or removing the bases downstream also reduce the binding significantly. This thesis goes on to characterize the structure of the CPSF30—hFip1 complex, which was not observed in the previous EM structures of the mPSF. It was known that CPSF30 ZF4–ZF5 recruits the hFip1 subunit of CPSF, although the details of this interaction have not been characterized. Here we report the crystal structure of human CPSF30 ZF4–ZF5 in complex with residues 161–200 of hFip1 at 1.9 Å. Unexpectedly, the structure reveals one hFip1 molecule binding to each ZF4 and ZF5, with a conserved mode of interaction. Mutagenesis studies confirm that the CPSF30–hFip1 complex has 1:2 stoichiometry in vitro. Mutation of each binding site in CPSF30 still allows one copy of hFip1 to bind, while mutation of both sites abrogates binding. Our fluorescence polarization binding assays show that ZF4 has higher affinity for hFip1, with a Kd of 1.8 nM. We also demonstrate that two copies of the catalytic module of poly(A) polymerase (PAP) are recruited by the CPSF30–hFip1 complex in vitro, and both hFip1 binding sites in CPSF30 can support polyadenylation.
Subjects/Keywords: Biochemistry; Biophysics; Messenger RNA – Analysis; Mutagenesis
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Hamilton, K. (2021). Structural and Biochemical Studies of the Human pre-mRNA 3’-end Processing Complex. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/d8-6xaw-xv26
Chicago Manual of Style (16th Edition):
Hamilton, Keith. “Structural and Biochemical Studies of the Human pre-mRNA 3’-end Processing Complex.” 2021. Doctoral Dissertation, Columbia University. Accessed February 27, 2021.
https://doi.org/10.7916/d8-6xaw-xv26.
MLA Handbook (7th Edition):
Hamilton, Keith. “Structural and Biochemical Studies of the Human pre-mRNA 3’-end Processing Complex.” 2021. Web. 27 Feb 2021.
Vancouver:
Hamilton K. Structural and Biochemical Studies of the Human pre-mRNA 3’-end Processing Complex. [Internet] [Doctoral dissertation]. Columbia University; 2021. [cited 2021 Feb 27].
Available from: https://doi.org/10.7916/d8-6xaw-xv26.
Council of Science Editors:
Hamilton K. Structural and Biochemical Studies of the Human pre-mRNA 3’-end Processing Complex. [Doctoral Dissertation]. Columbia University; 2021. Available from: https://doi.org/10.7916/d8-6xaw-xv26
18.
Michaels, Mary Jessamine.
Identification of body fluids by mRNA analysis with minion nanopore sequencing.
Degree: 2018, NC Docks
URL: http://libres.uncg.edu/ir/wcu/f/Michaels2018.pdf
► The identification of body fluids present on evidence items in a criminal investigation can be vital to understanding the nature of a crime, particularly in…
(more)
▼ The identification of body fluids present on evidence items in a criminal investigation can be vital to understanding the nature of a crime, particularly in cases of sexual assault. Although crime labs can confirm the presence of body fluids like semen and blood on a piece of evidence using traditional serological techniques, they cannot confirm the presence of saliva or vaginal fluid or differentiate peripheral blood from menstrual blood. Due to the unique patterns of gene expression in different cell types, different body fluids contain distinct messenger RNA (mRNA) molecules, which can be analyzed to generate mRNA profiles for confirmatory identification of body fluids. High throughput sequencing methods present the opportunity to generate large amounts of data from low level forensic samples that is not achievable with more traditional techniques. In this study, the MinION sequencer by Oxford Nanopore Technologies (ONT), which is a small and affordable high throughput sequencer that generates data rapidly and in real time, was assessed to determine its ability to generate high quality data from forensic type samples. Semen, saliva, blood, vaginal fluid, and menstrual blood from eight different donors were collected on sterile swabs. Additionally, a tenfold dilution series was performed on semen, blood, and saliva samples from three donors each and decreasing volumes of semen were pipetted onto vaginal swabs from three sets of donors. DNA and RNA were co-extracted from half swabs. DNA fractions were taken forward for short tandem repeat (STR) analysis. For RNA fractions, cDNA was generated, and a multiplex PCR targeting two genes per body fluid was performed. Amplicons were sequenced on the MinION with the 1D Ligation Sequencing Kit by ONT. Full DNA profiles were obtained for all semen, blood, and menstrual blood samples, and most of the saliva and vaginal fluid samples. Profiles were obtained for diluted semen, saliva, and blood samples, and mixed profiles were obtained for the semen/vaginal fluid mixture samples. The multiplex PCR was highly specific for each body fluid, with little to no cross reactivity. The MinION was able to obtain at least 1,000X coverage of target genes and little to no off target reads, even for some diluted samples. Both vaginal fluid and semen genes were detected in mixture samples. Optimization of the MinION sequencing workflow to maximize read counts and minimize costs should be explored. Despite the high input requirements stated by ONT for sequencing, the MinION appears to be able to generate high quality data with lower DNA/RNA input.
Subjects/Keywords: Body fluids – Analysis; Messenger RNA – Analysis; Messenger RNA – Biotechnology; DNA fingerprinting; Forensic genetics – Technique
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Michaels, M. J. (2018). Identification of body fluids by mRNA analysis with minion nanopore sequencing. (Thesis). NC Docks. Retrieved from http://libres.uncg.edu/ir/wcu/f/Michaels2018.pdf
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Michaels, Mary Jessamine. “Identification of body fluids by mRNA analysis with minion nanopore sequencing.” 2018. Thesis, NC Docks. Accessed February 27, 2021.
http://libres.uncg.edu/ir/wcu/f/Michaels2018.pdf.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Michaels, Mary Jessamine. “Identification of body fluids by mRNA analysis with minion nanopore sequencing.” 2018. Web. 27 Feb 2021.
Vancouver:
Michaels MJ. Identification of body fluids by mRNA analysis with minion nanopore sequencing. [Internet] [Thesis]. NC Docks; 2018. [cited 2021 Feb 27].
Available from: http://libres.uncg.edu/ir/wcu/f/Michaels2018.pdf.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Michaels MJ. Identification of body fluids by mRNA analysis with minion nanopore sequencing. [Thesis]. NC Docks; 2018. Available from: http://libres.uncg.edu/ir/wcu/f/Michaels2018.pdf
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Texas Southwestern Medical Center
19.
Irnov.
Regulatory RNAs at the Heart of Sugar Metabolism: New Mechanisms and Novel Discoveries.
Degree: 2011, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/854
► Bacteria are adept at using a variety of posttranscriptional strategies to regulate gene expression. Specifically, various RNA-mediated genetic control elements have been discovered in the…
(more)
▼ Bacteria are adept at using a variety of posttranscriptional strategies to regulate gene expression. Specifically, various
RNA-mediated genetic control elements have been discovered in the past decade through a combination of genetics, bioinformatics, and transcriptomic approaches. Together, these
RNA elements control the expression of many genes involved in diverse cellular processes such as energy metabolism, stress response, biofilm formation, and pathogenesis. In the Gram-positive bacterium Bacillus subtilis, several
RNA elements have been shown to be required for the precise coordination of genes involved in various sugar utilization pathways. These genetic switches typically regulate gene expression by modulating the formation of a transcription termination element in a ligand-dependent manner. Interestingly, two unique elements, the glmS ribozyme and the eps-associated
RNA (EAR), are missing the signature elements required for control of transcription termination or translation initiation. The latter mechanism is more commonly found in Gram-negative bacteria. Our objective is to study the mechanisms by which these two RNAs control gene expression. Additionally, we would like to identify other regulatory RNAs that are important for sugar metabolism in Bacillus subtilis.
Both the glmS ribozyme and EAR are positioned at the center of the sugar metabolism pathways in B. subtilis. The glmS
RNA is a glucosamine-6-phosphate responsive element that regulates the expression of the GlmS enzyme, which directs sugar precursors from glycolysis into the cell wall biosynthesis pathway. The EAR element resides within the 16-kb eps operon that is required for biofilm exopolysaccharide production. Our data demonstrates that both RNAs employ novel mechanisms: the glmS ribozyme utilizes a ligand-specific RNase-mediated degradation event, while EAR uses a processive antitermination mechanism for complete synthesis of the long operon. Furthermore, by using high-throughput sequencing approach we have successfully identified many new regulatory
RNA candidates, including various long 5`-UTR, toxin-antitoxin systems, prophage-encoded RNAs, and several developmentally regulated small RNAs. Their functions are still under investigation.
Collectively, our studies provide important insights into the different aspects of bacterial physiology, including
RNA decay pathways, transcription of long operons and cellular differentiation. We argue that posttranscriptional regulation is of greater importance to Bacillus subtilis (and probably all bacteria) than previously realized.
Advisors/Committee Members: Winkler, Wade C..
Subjects/Keywords: Bacterial Proteins; RNA, Bacterial; RNA, Messenger; Genetic Transcription
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Irnov. (2011). Regulatory RNAs at the Heart of Sugar Metabolism: New Mechanisms and Novel Discoveries. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/854
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Irnov. “Regulatory RNAs at the Heart of Sugar Metabolism: New Mechanisms and Novel Discoveries.” 2011. Thesis, University of Texas Southwestern Medical Center. Accessed February 27, 2021.
http://hdl.handle.net/2152.5/854.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Irnov. “Regulatory RNAs at the Heart of Sugar Metabolism: New Mechanisms and Novel Discoveries.” 2011. Web. 27 Feb 2021.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Vancouver:
Irnov. Regulatory RNAs at the Heart of Sugar Metabolism: New Mechanisms and Novel Discoveries. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2011. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/2152.5/854.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Irnov. Regulatory RNAs at the Heart of Sugar Metabolism: New Mechanisms and Novel Discoveries. [Thesis]. University of Texas Southwestern Medical Center; 2011. Available from: http://hdl.handle.net/2152.5/854
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

Columbia University
20.
Tan, Dazhi.
Molecular Basis for the Recognition of the Regulatory Stem-loop Structures in Eukaryotic Messenger RNAs.
Degree: 2014, Columbia University
URL: https://doi.org/10.7916/D8FN14B4
► Apart from carrying genetic information, RNAs also act as effectors of cellular processes through folding into intricate secondary and tertiary structures. The ubiquitous RNA structures…
(more)
▼ Apart from carrying genetic information, RNAs also act as effectors of cellular processes through folding into intricate secondary and tertiary structures. The ubiquitous RNA structures in eukaryotic mRNAs, in collaboration with specific RNA-binding proteins, control many aspects of the post-transcriptional regulation of gene expression. However, the molecular bases for the recognition of these mRNA structures by their protein partners remain poorly understood due to the lack of structural information.
This dissertation presents our structural studies on two protein-RNA complexes that both include regulatory mRNA stem-loop structures. We first describe the crystal structure of a ternary complex including the highly conserved human histone mRNA stem-loop (SL), the stem-loop binding protein (SLBP) and the 3′ to 5′ exonuclease 3′hExo. This structure identifies a single sequence-specific interaction between the SL and SLBP, and the mostly shape-dependent RNA-recognition mode by both proteins. In addition to explaining the large body of biochemical and biophysical data on this complex accumulated over the last two decades, we also for the first time elucidate the induced-fit mechanism underlying the cooperativity between SLBP and 3′hExo. We next shift our focus to a class of less conserved mRNA stem-loop structures named constitutive decay elements (CDE). The RNA-binding ROQ domain of Roquin recognizes the various CDEs and mediates the decay of CDE-containing mRNAs, which predominantly encode proteins responsible for inflammation and autoimmunity. Structural and biochemical studies of the ROQ domain in complex with two different CDE RNAs unexpectedly reveal two distinct RNA binding sites on this protein, one recognizing CDE stem-loops and the other binding to double-stranded RNAs. The stuctures are also in agreement with the versatility of Roquin and have opened up new avenues to investigating its functions in modulating the stability of target mRNAs.
Subjects/Keywords: Messenger RNA; RNA-protein interactions; Eukaryotic cells; Biology; Biochemistry; Molecular biology
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Tan, D. (2014). Molecular Basis for the Recognition of the Regulatory Stem-loop Structures in Eukaryotic Messenger RNAs. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/D8FN14B4
Chicago Manual of Style (16th Edition):
Tan, Dazhi. “Molecular Basis for the Recognition of the Regulatory Stem-loop Structures in Eukaryotic Messenger RNAs.” 2014. Doctoral Dissertation, Columbia University. Accessed February 27, 2021.
https://doi.org/10.7916/D8FN14B4.
MLA Handbook (7th Edition):
Tan, Dazhi. “Molecular Basis for the Recognition of the Regulatory Stem-loop Structures in Eukaryotic Messenger RNAs.” 2014. Web. 27 Feb 2021.
Vancouver:
Tan D. Molecular Basis for the Recognition of the Regulatory Stem-loop Structures in Eukaryotic Messenger RNAs. [Internet] [Doctoral dissertation]. Columbia University; 2014. [cited 2021 Feb 27].
Available from: https://doi.org/10.7916/D8FN14B4.
Council of Science Editors:
Tan D. Molecular Basis for the Recognition of the Regulatory Stem-loop Structures in Eukaryotic Messenger RNAs. [Doctoral Dissertation]. Columbia University; 2014. Available from: https://doi.org/10.7916/D8FN14B4

Columbia University
21.
Jurado, Ashley Rae.
Structural Studies of the Fungal pre-mRNA 3'-end Processing Machinery.
Degree: 2015, Columbia University
URL: https://doi.org/10.7916/D8W094VC
► During mRNA synthesis, pre-mRNAs must be cleaved and polyadenylated at their 3'-end to be fully mature, before being exported from the nucleus. In yeast, there…
(more)
▼ During mRNA synthesis, pre-mRNAs must be cleaved and polyadenylated at their 3'-end to be fully mature, before being exported from the nucleus. In yeast, there is a large protein machinery comprised of dozens of proteins that work together to perform these two reactions. Some of these proteins are capable of recognizing and binding key sequence elements in the pre-mRNA, effectively directing where in the transcript the cleavage and polyadenylation occur. In this thesis, recently reported structural findings related to the pre-mRNA 3'-end processing machinery are summarized. Within this machinery, the Cleavage Factor IA (CF-IA) complex is comprised of the Rna14, Rna15, and Pcf11 and Clp1 proteins. Results reported here include the crystal structure of the Rna14-Rna15 complex, which indicates that the Rna14 protein forms a dimer that has inherent conformational variability. The Rna15 protein binds to the C-terminal domain of Rna14, and is connected to the Rna14 HAT domain by a flexible linker, which may indicate that Rna15 functions somewhat independently of the Rna14 HAT domain. The complete CF-IA complex is explored in detail, including protein-protein interactions within the complex and the stoichiometric ratios of CF-IA components. Unlike previous reports, results indicate that CF-IA may form a dimer with a 2:2:2:2 stoichiometry of Rna14:Rna15:Clp1:Pcf11. Also reported are projects unrelated to CF-IA, including the crystal structure of the biotin-dependent alpha(6)beta(6) geranyl-CoA carboxylase (GCC) holoenzyme. Comparison of GCC to the closely related 3-methylcrotonyl CoA carboxylase (MCC) holoenzyme reveals a conserved domain swap in the carboxyltransferase (CT) domains of both enzymes. This domain swap is not present in the related biotin-dependent carboxylases propionyl-CoA carboxylase (PCC) and acetyl-CoA carboxylase (ACC), which may indicate a distinct lineage for biotin-dependent carboxylases that target the γ-carbon. In addition, comparison of the two structures also reveals a conserved Phe191 in MCC that is absent in GCC. Phe191 blocks a key substrate-binding pocket and explains the differences in substrate-specificities between MCC and GCC. The role of Phe191 is tested by site-directed mutagenesis to a Glycine to open the pocket in MCC and by mutating a structurally equivalent Glycine to Phe to close the pocket in GCC. These mutations can convert MCC to a GCC and vice versa.
Subjects/Keywords: Proteins; RNA splicing; Scission (Chemistry); Messenger RNA; Molecular biology; Biology; Biochemistry
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Jurado, A. R. (2015). Structural Studies of the Fungal pre-mRNA 3'-end Processing Machinery. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/D8W094VC
Chicago Manual of Style (16th Edition):
Jurado, Ashley Rae. “Structural Studies of the Fungal pre-mRNA 3'-end Processing Machinery.” 2015. Doctoral Dissertation, Columbia University. Accessed February 27, 2021.
https://doi.org/10.7916/D8W094VC.
MLA Handbook (7th Edition):
Jurado, Ashley Rae. “Structural Studies of the Fungal pre-mRNA 3'-end Processing Machinery.” 2015. Web. 27 Feb 2021.
Vancouver:
Jurado AR. Structural Studies of the Fungal pre-mRNA 3'-end Processing Machinery. [Internet] [Doctoral dissertation]. Columbia University; 2015. [cited 2021 Feb 27].
Available from: https://doi.org/10.7916/D8W094VC.
Council of Science Editors:
Jurado AR. Structural Studies of the Fungal pre-mRNA 3'-end Processing Machinery. [Doctoral Dissertation]. Columbia University; 2015. Available from: https://doi.org/10.7916/D8W094VC

Columbia University
22.
Bailey, Nevette Adia.
Dynamics of Translation Elongation in an mRNA Context with a High Frameshifting Propensity.
Degree: 2019, Columbia University
URL: https://doi.org/10.7916/d8-qsnc-d250
► Ribosomes are universally conserved macromolecular machines found within all living cells that catalyze protein synthesis, one of nature’s most fundamental processes. Ribosomes synthesize proteins, which…
(more)
▼ Ribosomes are universally conserved macromolecular machines found within all living cells that catalyze protein synthesis, one of nature’s most fundamental processes. Ribosomes synthesize proteins, which are polymeric chains of amino acids, by incorporating the amino acids one at a time via aminoacylated-transfer RNAs (aa-tRNAs), based on translation of the sequence of triplet- nucleotide codons presented by the messenger RNA (mRNA) template that is a direct readout of genomic DNA. Recent biochemical, structural, dynamic, and computational studies have uncovered large-scale conformational changes of the ribosome, its tRNA substrates, and the additional protein translation factors that play important roles in regulating protein synthesis, especially during the elongation phase of translation when the bulk of each protein is synthesized. How the ribosome, its translation elongation factors, tRNAs, and mRNA physically coordinate and regulate the movements of the tRNAs carrying amino acids into, through, and out of the ribosome remains one of the more fundamental questions in the mechanistic studies of protein synthesis. A complete understanding of the conformational dynamics of ribosomal complexes will improve our knowledge of how translation is regulated, including how ribosome-targeting antibiotics regulate translation elongation, and will provide crucial information for designing next-generation antibiotics. In this thesis I have investigated the conformational dynamics of the ribosome during the elongation phase of protein synthesis at the single-molecule level using single-molecule fluorescence resonance energy transfer (smFRET) microscopy experiments. Specifically, I have studied ribosomal dynamics during the elongation phase of translation in the presence of a tRNAPro in the context of an mRNA that has the propensity to shift out of the reading frame. My studies have revealed information about the mechanistic and regulatory functions of the posttranscriptional modifications of tRNAPro in a context in which the ribosomal complex has the propensity to undergo non-programmed +1-frameshifting, in which the tRNA-mRNA base pairing shifts one base toward the 3’ end of the mRNA, and if unchecked, leads to the synthesis of a polypeptide with a completely different sequence of amino acids. My data suggests that in this context, the mechanism underlying non-programmed +1-frameshifting involves the tRNA shifting out of frame prior to the tRNA being accommodated in the P site, i.e. either while the tRNA is in the A site, or more likely, during translocation of the tRNA from the A site to the P site, and not while the tRNA is already occupying the P site, as previously proposed.
Subjects/Keywords: Biophysics; Ribosomes; Proteins – Synthesis; Genetic translation; Messenger RNA; Transfer RNA
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Bailey, N. A. (2019). Dynamics of Translation Elongation in an mRNA Context with a High Frameshifting Propensity. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/d8-qsnc-d250
Chicago Manual of Style (16th Edition):
Bailey, Nevette Adia. “Dynamics of Translation Elongation in an mRNA Context with a High Frameshifting Propensity.” 2019. Doctoral Dissertation, Columbia University. Accessed February 27, 2021.
https://doi.org/10.7916/d8-qsnc-d250.
MLA Handbook (7th Edition):
Bailey, Nevette Adia. “Dynamics of Translation Elongation in an mRNA Context with a High Frameshifting Propensity.” 2019. Web. 27 Feb 2021.
Vancouver:
Bailey NA. Dynamics of Translation Elongation in an mRNA Context with a High Frameshifting Propensity. [Internet] [Doctoral dissertation]. Columbia University; 2019. [cited 2021 Feb 27].
Available from: https://doi.org/10.7916/d8-qsnc-d250.
Council of Science Editors:
Bailey NA. Dynamics of Translation Elongation in an mRNA Context with a High Frameshifting Propensity. [Doctoral Dissertation]. Columbia University; 2019. Available from: https://doi.org/10.7916/d8-qsnc-d250

University of Hong Kong
23.
陳燕彤.
Demonstration of specific
physical interaction between CHOP mRNA and intracellular
proteins.
Degree: 2011, University of Hong Kong
URL: http://hdl.handle.net/10722/174332
► The ability of a cell to respond precisely to environmental stress depends on the expression of a large number of genes in a finely coordinated…
(more)
▼ The ability of a cell to respond precisely to
environmental stress depends on the expression of a large number of
genes in a finely coordinated manner. One of such genes is CHOP
that encodes the CCAAT/Enhancer-Binding Protein Homologous Protein.
CHOP is usually expressed to mediate apoptosis under the condition
of excessive stress. The expression of CHOP therefore has to be
stringently regulated as its expression will determine the fate of
a cell under stress. The expression of many genes is regulated at
the posttranscriptional level through the metabolism of their mRNA,
such as maturation, transport, storage, and degradation of mRNA.
Many metabolic processes of mRNA are known to be mediated by
RNA-binding proteins that specifically interact with the mRNA.
RNA-binding proteins that interact with the CHOP mRNA have until
present not been identified. The aim of this study is to
investigate what proteins may bind specifically to CHOP mRNA. The
study will enable further understanding regarding how the
expression of CHOP is regulated in cellular stress response.
Proteins extracted from HeLa cells were incubated with a 335bp
[3H]-labelled CHOP
RNA probe that spans over a part of the coding
region and the 3’UTR of CHOP mRNA. Sucrose density gradient
ultracentrifugation revealed that after incubation with proteins
extracted from HeLa cells, the sedimentation rate of the [3H]-CHOP
RNA probe was significantly higher than that of the free [3H]-
RNA
probe. The formation of heavy molecular complexes involving the
[3H]-CHOP
RNA probe was therefore suggested. However, no increase
in sedimentation rate of the [3H]-CHOP
RNA probe was observed in
the presence of an excess of unlabelled CHOP
RNA probe. Similar
observations were made when the experiments were performed using
proteins isolated from cells treated with As2O3. Two putative
sequence elements, the Adenylate-Uridylate-Rich Element (ARE) and
the Putative Regulatory Element (PRE) located respectively in the
3’UTR and coding region of the CHOP mRNA were then examined for
their involvement in
RNA-protein interaction. The deletion of ARE
and/or PRE, from the [3H]-CHOP
RNA probe had little effect on the
binding of the
RNA probe to the HeLa cell proteins. Consistently,
unlabelled CHOP
RNA probes with the same deletions were only
slightly weaker in competing with the intact [3H]-CHOP
RNA probe to
bind to HeLa cell proteins. Human Antigen R (HuR) was identified by
Western blot analysis to be present in the proteins that were
obtained by pull-down assays using biotinylated CHOP
RNA as a
probe. The deletion of ARE and/or PRE resulted in a slight
reduction of HuR obtained by pull down assays. This study provides
the first evidence that physical binding interaction occurs between
intracellular
RNA-binding proteins and CHOP mRNA. More importantly,
one such protein is HuR. Data suggest that HuR binding to the CHOP
mRNA is mediated by sequences in the CHOP mRNA other than ARE and
PRE.
Advisors/Committee Members: Wong, NS (advisor).
Subjects/Keywords: Messenger RNA.;
RNA-protein interactions.
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
陳燕彤.. (2011). Demonstration of specific
physical interaction between CHOP mRNA and intracellular
proteins. (Thesis). University of Hong Kong. Retrieved from http://hdl.handle.net/10722/174332
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
陳燕彤.. “Demonstration of specific
physical interaction between CHOP mRNA and intracellular
proteins.” 2011. Thesis, University of Hong Kong. Accessed February 27, 2021.
http://hdl.handle.net/10722/174332.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
陳燕彤.. “Demonstration of specific
physical interaction between CHOP mRNA and intracellular
proteins.” 2011. Web. 27 Feb 2021.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Vancouver:
陳燕彤.. Demonstration of specific
physical interaction between CHOP mRNA and intracellular
proteins. [Internet] [Thesis]. University of Hong Kong; 2011. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/10722/174332.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
陳燕彤.. Demonstration of specific
physical interaction between CHOP mRNA and intracellular
proteins. [Thesis]. University of Hong Kong; 2011. Available from: http://hdl.handle.net/10722/174332
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

University of Texas Southwestern Medical Center
24.
Lee, Chien-Der.
Switching the Fate of mRNAs for Mitochondrial Biogenesis.
Degree: 2017, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/7085
► The general metadata – e.g., title, author, abstract, subject headings, etc. – is publicly available, but access to the submitted files is restricted to UT…
(more)
▼ The general metadata – e.g., title, author, abstract, subject headings, etc. – is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.
mRNAs encoding mitochondrial biogenesis proteins are co-regulated in a manner closely linked to metabolism. In yeast growing in glucose, mitochondrial biogenesis is repressed, but must be induced upon glucose depletion to enable energy production using alternative carbon sources such as ethanol or acetate through mitochondrial respiration. Yeast cells growing in glucose constitutively transcribe nuclear-encoded mitochondrial ribosomal mRNAs at a basal level. However, instead of sharing a common upstream activating sequence for transcription, those mRNAs all harbor a common sequence motif within their 3'UTRs. Puf3p, an RNA-binding protein, can directly bind to this class of mRNA transcripts to promote degradation in glucose medium. However, the function of Puf3p upon glucose depletion is not clear.
In the first part of this study, I show how Puf3p responds to glucose availability to switch the fate of its bound transcripts that encode proteins required for mitochondrial biogenesis. This regulation allows cell to quickly respond to glucose depletion by switching the degradation fate of those mRNAs to translation. Thus, yeast can activate pre-existing mRNA without relying on de novo transcription for mitochondrial biogenesis. I then show Puf3p is subjected to phosphorylation downstream of a glucose sensing pathway. Puf3p is hypophosphorylated in glucose medium; however, upon glucose depletion, Puf3p becomes heavily phosphorylated within its N-terminal region of low complexity, associates with polysomes, and promotes translation of its target mRNAs.
In the second part of this study, I show that phosphorylation of Puf3p is required for translational activation of its bound mRNAs. Strikingly, a Puf3p mutant that prevents its phosphorylation no longer promotes mRNA translation but also becomes trapped in intracellular foci in an mRNA-dependent manner. These findings suggest how the inability to properly resolve Puf3p-containing RNA-protein granules via a phosphorylation-based mechanism might be toxic to a cell. The toxicity might be due to sequestration of translational factors in the Puf3p RNA protein granule in a manner reminiscent of neurodegenerative disease-related protein aggregation.
Advisors/Committee Members: Liu, Yi, Tu, Benjamin, McKnight, Steven L., Conrad, Nicholas.
Subjects/Keywords: Glucose; RNA, Messenger; RNA-Binding Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lee, C. (2017). Switching the Fate of mRNAs for Mitochondrial Biogenesis. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/7085
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Lee, Chien-Der. “Switching the Fate of mRNAs for Mitochondrial Biogenesis.” 2017. Thesis, University of Texas Southwestern Medical Center. Accessed February 27, 2021.
http://hdl.handle.net/2152.5/7085.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lee, Chien-Der. “Switching the Fate of mRNAs for Mitochondrial Biogenesis.” 2017. Web. 27 Feb 2021.
Vancouver:
Lee C. Switching the Fate of mRNAs for Mitochondrial Biogenesis. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2017. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/2152.5/7085.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Lee C. Switching the Fate of mRNAs for Mitochondrial Biogenesis. [Thesis]. University of Texas Southwestern Medical Center; 2017. Available from: http://hdl.handle.net/2152.5/7085
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Texas Southwestern Medical Center
25.
Esparza, Matthew Aaron.
Chemical Intervention of Influenza Virus mRNA Nuclear Export.
Degree: 2020, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/8811
► Influenza A viruses are human pathogens with limited therapeutic options, making it crucial to devise strategies for the identification of new classes of antiviral medications.…
(more)
▼ Influenza A viruses are human pathogens with limited therapeutic options, making it crucial to devise strategies for the identification of new classes of antiviral medications. The influenza A virus genome is constituted of 8
RNA segments. Two of these viral RNAs are transcribed into mRNAs that are alternatively spliced. The M1 mRNA encodes the M1 protein but is also alternatively spliced to yield the M2 mRNA during infection. M1 to M2 mRNA splicing occurs at nuclear speckles, and M1 and M2 mRNAs are exported to the cytoplasm for translation. M1 and M2 proteins are critical for viral trafficking, assembly, and budding. We show that influenza virus utilizes nuclear speckles to promote post-transcriptional splicing of its M1 mRNA. We assign previously unknown roles for the viral NS1 protein and cellular factors to an intranuclear trafficking pathway that targets the viral M1 mRNA to nuclear speckles, mediates splicing at these nuclear bodies, and exports the spliced M2 mRNA from the nucleus. In addition, gene knockout of the cellular protein NS1-BP, a constituent of the M mRNA speckle-export pathway, inhibits M mRNA nuclear export without significantly altering bulk cellular mRNA export, providing an avenue to preferentially target influenza virus. We performed a high-content, image-based chemical screen using single-molecule
RNA-FISH to label viral M mRNAs followed by multistep quantitative approaches to assess cellular mRNA and cell toxicity. We identified inhibitors of viral mRNA biogenesis and nuclear export that exhibited no significant activity towards bulk cellular mRNA at non-cytotoxic concentrations. Among the hits is a small molecule that inhibits nuclear export of a subset of viral and cellular mRNAs via the mRNA export factor UAP56 without altering bulk cellular mRNA nuclear export. These findings underscore specific nuclear export requirements for viral mRNA nuclear export. This
RNA export inhibitor also impaired replication of diverse influenza virus strains at non-toxic concentrations. Thus, this screening strategy yielded compounds that alone or in combination may serve as leads to new ways of treating influenza virus infection and are novel tools for studying viral
RNA trafficking in the nucleus.
Advisors/Committee Members: Shay, Jerry W., Fontoura, Beatriz, Grinnell, Frederick, Minna, John D..
Subjects/Keywords: Active Transport, Cell Nucleus; Influenza A virus; RNA Splicing; RNA, Messenger; RNA, Viral; Transcription Factors
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Esparza, M. A. (2020). Chemical Intervention of Influenza Virus mRNA Nuclear Export. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/8811
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Esparza, Matthew Aaron. “Chemical Intervention of Influenza Virus mRNA Nuclear Export.” 2020. Thesis, University of Texas Southwestern Medical Center. Accessed February 27, 2021.
http://hdl.handle.net/2152.5/8811.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Esparza, Matthew Aaron. “Chemical Intervention of Influenza Virus mRNA Nuclear Export.” 2020. Web. 27 Feb 2021.
Vancouver:
Esparza MA. Chemical Intervention of Influenza Virus mRNA Nuclear Export. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2020. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/2152.5/8811.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Esparza MA. Chemical Intervention of Influenza Virus mRNA Nuclear Export. [Thesis]. University of Texas Southwestern Medical Center; 2020. Available from: http://hdl.handle.net/2152.5/8811
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
26.
Zervakis, Konstantinos.
Μελέτη έκφρασης και προγνωστικής αξίας της Poly (ADP-ribose) Polymerase 1 mRNA στα μυελοδυσπλαστικά σύνδρομα.
Degree: 2019, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)
URL: http://hdl.handle.net/10442/hedi/45792
► Poly (ADP-ribose) polymerase 1 (PARP-1) has a central role in the repair of DNA breaks and is a promising treatment target in malignancy. We measured…
(more)
▼ Poly (ADP-ribose) polymerase 1 (PARP-1) has a central role in the repair of DNA breaks and is a promising treatment target in malignancy. We measured PARP1 mRNA levels by a SYBR-green-based PCR in the bone marrow of 74 patients with myelodysplastic syndrome (MDS) and correlated them to their demographic, hematologic and prognostic characteristics. The median PARP1 mRNA levels were correlated to the type of MDS (2008/2016 WHO classication, P = 0.005) and to the IPSS score (P = 0.002). A correlation was also found with the IPSS-R score (P = 0.011) and the cytogenetic risk (P = 0.008). In all cases, higher PARP1 levels were correlated with a higher risk category. Moreover, we found a signicant survival disadvantage for patients with high PARP1 levels (median survival of 37.4 months versus ‘not reached’ for low PARP1 levels, P = 0.0001, and a 5-year survival rate of 29.8 versus 88.9%, respectively). PARP1 mRNA levels were found to be the stronger predictor of survival in multivariate analysis. These correlations have never been reported in the past and may render PARP1 a prognostic factor to be incorporated in the current prognostic systems for MDS, also laying the basis for clinical trials evaluating PARP1 inhibitors in higher-risk MDS.
Η πολυμεράση της πολυ (ADP-ριβόζης) 1 (PARP-1) αποτελεί βασικό μέλος οικογένειας πυρηνικών ενζύμων που συμμετέχουν στην επιδιόρθωση του DNA και ήδη είναι θεραπευτικός στόχος σε συμπαγείς όγκους. Στην παρούσα μελέτη ποσοτικοποιήθηκαν τα επίπεδα έκφρασης του mRNA της PARP1 με ποσοτική PCR (qpcr) και τη μέθοδο SYBR στον μυελό των οστών 74 ασθενών με διάγνωση μυελοδυσπλαστικού συνδρόμου (MDS). Τα επίπεδα έκφρασης του mRNA της PARP1 αποτυπώθηκαν με τη μορφή του λόγου των μεταγράφων parp1/actin και συσχετίστηκαν με τα δημογραφικά, αιματολογικά και προγνωστικά χαρακτηριστικά των ασθενών. Τα αποτελέσματα εκφράστηκαν ως διάμεσος ± απόκλιση λάθους (median± SEM). Τα επίπεδα έκφρασης του mRNA της PARP1 συσχετίστηκαν στη συνέχεια με τον τύπο MDS (ταξινόμηση WHO 2008/2016, p = 0.005) και με το IPSS score (p = 0.002). Επίσης, διαπιστώθηκε συσχέτιση με το IPSS-R (p = 0,011) και την προγνωστική σημασία των κυτταρογενετικών ευρημάτων (p = 0,008). Σε όλες τις περιπτώσεις, υψηλότερα επίπεδα PARP1 συσχετίστηκαν με υψηλότερη κατηγορία κινδύνου. Επιπλέον, διαπιστώθηκε ένα στατιστικά σημαντικό μειονέκτημα επιβίωσης για τους ασθενείς με υψηλά επίπεδα PARP1 ( η διάμεση επιβίωση ασθενών ήταν 37,4 μήνες, ενώ η διάμεση επιβίωση ασθενών με χαμηλά επίπεδα PARP1 δεν επιτεύχθηκε, p = 0,0001). Η επιβίωση στα 5 χρόνια ήταν 29,8% έναντι 88,9% αντίστοιχα. Τα επίπεδα mRNA της PARP1 βρέθηκαν να είναι ο ισχυρότερος προγνωστικός παράγοντας της επιβίωσης σε ανάλυση πολλαπλών μεταβλητών. Αυτές οι συσχετίσεις δεν έχουν αναφερθεί ποτέ στο παρελθόν και μπορεί να καταστήσουν την PARP1 έναν προγνωστικό παράγοντα που μπορεί να ενσωματωθεί στα τρέχοντα προγνωστικά συστήματα για το MDS, θέτοντας επίσης τη βάση για τις κλινικές δοκιμές που αξιολογούν τους αναστολείς PARP1 σε MDS υψηλού κινδύνου.
Subjects/Keywords: Μυελοδυσπλαστικά σύνδρομα (MDS); Poly (ADP-Ribose) Polymerase-1; RNA, messenger; Poly (ADP-Ribose) Polymerase-1; Myelodysplastic syndromes; RNA, messenger
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zervakis, K. (2019). Μελέτη έκφρασης και προγνωστικής αξίας της Poly (ADP-ribose) Polymerase 1 mRNA στα μυελοδυσπλαστικά σύνδρομα. (Thesis). National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Retrieved from http://hdl.handle.net/10442/hedi/45792
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Zervakis, Konstantinos. “Μελέτη έκφρασης και προγνωστικής αξίας της Poly (ADP-ribose) Polymerase 1 mRNA στα μυελοδυσπλαστικά σύνδρομα.” 2019. Thesis, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Accessed February 27, 2021.
http://hdl.handle.net/10442/hedi/45792.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Zervakis, Konstantinos. “Μελέτη έκφρασης και προγνωστικής αξίας της Poly (ADP-ribose) Polymerase 1 mRNA στα μυελοδυσπλαστικά σύνδρομα.” 2019. Web. 27 Feb 2021.
Vancouver:
Zervakis K. Μελέτη έκφρασης και προγνωστικής αξίας της Poly (ADP-ribose) Polymerase 1 mRNA στα μυελοδυσπλαστικά σύνδρομα. [Internet] [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2019. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/10442/hedi/45792.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Zervakis K. Μελέτη έκφρασης και προγνωστικής αξίας της Poly (ADP-ribose) Polymerase 1 mRNA στα μυελοδυσπλαστικά σύνδρομα. [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2019. Available from: http://hdl.handle.net/10442/hedi/45792
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Florida
27.
Yao, Bing.
GW182 Silences microRNA Targets by Divergent Functional Domains and Regulates microRNA Stability.
Degree: PhD, Medical Sciences - Molecular Cell Biology (IDP), 2012, University of Florida
URL: https://ufdc.ufl.edu/UFE0044363
► MicroRNA (miRNA) is a relatively new class of shortendogenous non-coding RNA. MiRNA can pair to the 3’ untranslated region ofmRNA. This interaction inactivates protein translation…
(more)
▼ MicroRNA (miRNA) is a relatively new class of shortendogenous non-coding
RNA. MiRNA can pair to the 3’ untranslated region ofmRNA. This interaction inactivates protein translation from the mRNA, andeventually triggers mRNA decay. All important cellular processes are known tobe regulated in part by miRNA. Aberrant expression of miRNA often associateswith a variety of diseases including cancer. The goal of my dissertationresearch is to understand the miRNA silencing mechanism, identify andcharacterize key protein players in this process, and elucidate how the maturemiRNA level is regulated. These discoveries will expand our knowledge inunderstanding this key post-transcriptional gene regulation pathway and offerthe possibility in developing miRNA-mediated therapeutic approaches. GW182 is an 182kDaprotein with multiple glycine/tryptophan repeats (GW or WG) playing a centralrole in miRNA-mediated gene silencing. GW182 interacts with its functionalpartner Argonaute proteins (AGO) via multiple domains to exert its silencingactivity. Using tethering functional assays, we identified two non-overlappingGW182 silencing domains, namely , induced primarily translationalrepression rather than mRNA decay. GW orWG repeats on these two domains were critical for silencing activity. Thesedata implicated a dynamic and diversified role of GW182 in miRNA-mediated gene silencingconveyed by its silencing domains and further established GW182 as acentral player in silencing gene expression. Furthermore, we identified a newrole of GW182 in regulating miRNA stability aside from its silencing function.Depletion of GW182 reduced mature miRNA level in different time points andcaused impaired miRNA export through secretory vesicles termed exosomes. A3’-5’ exoribonuclease complex was identified to be responsible for the miRNAdegradation. These findings revealed a novel role of GW182 in regulating mature miRNA stability by binding to Argonaute proteins This work alsop supported of the importance of GW182 in miRNA-mediated silencing homeostasis. ( en )
Advisors/Committee Members: Chan, Edward K (committee chair), Zhou, Lei (committee member), Terada, Naohiro (committee member), Swanson, Maurice S (committee member), Kilberg, Michael S (committee member).
Subjects/Keywords: Exosomes; Journalism; Messenger RNA; MicroRNAs; Proteins; Repression; RNA; RNA stability; Small interfering RNA; Transfection; argonaute – gw182 – microrna
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Yao, B. (2012). GW182 Silences microRNA Targets by Divergent Functional Domains and Regulates microRNA Stability. (Doctoral Dissertation). University of Florida. Retrieved from https://ufdc.ufl.edu/UFE0044363
Chicago Manual of Style (16th Edition):
Yao, Bing. “GW182 Silences microRNA Targets by Divergent Functional Domains and Regulates microRNA Stability.” 2012. Doctoral Dissertation, University of Florida. Accessed February 27, 2021.
https://ufdc.ufl.edu/UFE0044363.
MLA Handbook (7th Edition):
Yao, Bing. “GW182 Silences microRNA Targets by Divergent Functional Domains and Regulates microRNA Stability.” 2012. Web. 27 Feb 2021.
Vancouver:
Yao B. GW182 Silences microRNA Targets by Divergent Functional Domains and Regulates microRNA Stability. [Internet] [Doctoral dissertation]. University of Florida; 2012. [cited 2021 Feb 27].
Available from: https://ufdc.ufl.edu/UFE0044363.
Council of Science Editors:
Yao B. GW182 Silences microRNA Targets by Divergent Functional Domains and Regulates microRNA Stability. [Doctoral Dissertation]. University of Florida; 2012. Available from: https://ufdc.ufl.edu/UFE0044363
28.
Sement, François.
Identification d'une Terminal Uridylyl Transférase impliquée dans la protection de l'extrémité 3' des ARNm déadénylés chez Arabidopsis thaliana : Identification of a terminal uridylyl transferase implicated in the protection of deadenylated messager RNAs 3' end in Arabidopsis thaliana.
Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2012, Université de Strasbourg
URL: http://www.theses.fr/2012STRAJ132
► Le travail présenté dans ce manuscrit a permis de définir un nouveau rôle de l’uridylation des ARNm en utilisant Arabidopsis comme organisme d’étude. L’uridylation des…
(more)
▼ Le travail présenté dans ce manuscrit a permis de définir un nouveau rôle de l’uridylation des ARNm en utilisant Arabidopsis comme organisme d’étude. L’uridylation des ARN est catalysée par des ARN nucléotidyltransférases de la famille des poly(A) polymérases non canoniques ou ncPAP. Parmi les 14 gènes codant pour des ncPAP chez Arabidopsis, nous avons identifié une terminale uridylyl transférase, TUT1, responsable de l’uridylation des ARNm. Nos résultats montrent que TUT1 uridyleles ARNm après une étape de déadénylation. Cette uridylation ne modifie pas la vitesse de dégradation des ARNm mais est essentielle pour prévenir l’attaque des extrémités 3’ des ARNm déadénylés par des activités 3’-5’ exoribonucléasiques et la formation de transcrits aberrants tronqués en 3’. De manière intéressante, cette protection par l’uridylation peut être détectée au niveau des polysomes. Une des fonctions biologiques de l’uridylation des ARNm consiste à établir une polarité de 5’ en 3’ de la dégradation des ARNm. Cette polarité pourrait être essentielle dans le cas d’une dégradation des ARNm en cours de traduction.
The work presented in this manuscript defines a new role of mRNA uridylation, using Arabidopsis as a model organism. RNA uridylation is catalyzed by RNA nucleotidyltransferases belonging to the non canonical poly(A) polymerase (ncPAP) family. Among the 14 genes encoding ncPAPs in Arabidopsis, we identified a terminal uridylyl transferase, TUT1, responsible for mRNA uridylation. Our results show that mRNAs are uridylated by TUT1 after a deadenylation step. Uridylation doesn’t modify mRNA degradation rates but is essential for deadenylated mRNA 3’ end protection against 3’- 5’ exoribonucleolytic attacks and to prevent 3’ truncated aberrant mRNA formation. Interestingly, this protection by uridylation is detected in polysomes. One biological function of mRNA uridylation is to establish a 5’-3’ mRNA degradation polarity that could be essential in the case of cotranslational mRNA decay.
Advisors/Committee Members: Gagliardi, Dominique (thesis director).
Subjects/Keywords: Uridylation; Arabidopsis; ARN messager; Dégradation des ARN; Uridylation; Arabidopsis; Messenger RNA; RNA degradation; 572.8
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sement, F. (2012). Identification d'une Terminal Uridylyl Transférase impliquée dans la protection de l'extrémité 3' des ARNm déadénylés chez Arabidopsis thaliana : Identification of a terminal uridylyl transferase implicated in the protection of deadenylated messager RNAs 3' end in Arabidopsis thaliana. (Doctoral Dissertation). Université de Strasbourg. Retrieved from http://www.theses.fr/2012STRAJ132
Chicago Manual of Style (16th Edition):
Sement, François. “Identification d'une Terminal Uridylyl Transférase impliquée dans la protection de l'extrémité 3' des ARNm déadénylés chez Arabidopsis thaliana : Identification of a terminal uridylyl transferase implicated in the protection of deadenylated messager RNAs 3' end in Arabidopsis thaliana.” 2012. Doctoral Dissertation, Université de Strasbourg. Accessed February 27, 2021.
http://www.theses.fr/2012STRAJ132.
MLA Handbook (7th Edition):
Sement, François. “Identification d'une Terminal Uridylyl Transférase impliquée dans la protection de l'extrémité 3' des ARNm déadénylés chez Arabidopsis thaliana : Identification of a terminal uridylyl transferase implicated in the protection of deadenylated messager RNAs 3' end in Arabidopsis thaliana.” 2012. Web. 27 Feb 2021.
Vancouver:
Sement F. Identification d'une Terminal Uridylyl Transférase impliquée dans la protection de l'extrémité 3' des ARNm déadénylés chez Arabidopsis thaliana : Identification of a terminal uridylyl transferase implicated in the protection of deadenylated messager RNAs 3' end in Arabidopsis thaliana. [Internet] [Doctoral dissertation]. Université de Strasbourg; 2012. [cited 2021 Feb 27].
Available from: http://www.theses.fr/2012STRAJ132.
Council of Science Editors:
Sement F. Identification d'une Terminal Uridylyl Transférase impliquée dans la protection de l'extrémité 3' des ARNm déadénylés chez Arabidopsis thaliana : Identification of a terminal uridylyl transferase implicated in the protection of deadenylated messager RNAs 3' end in Arabidopsis thaliana. [Doctoral Dissertation]. Université de Strasbourg; 2012. Available from: http://www.theses.fr/2012STRAJ132

University of Texas Southwestern Medical Center
29.
Miller, Jason Brian.
The Design, Synthesis, and Evaluation of Zwitterionic and Cationic Lipids for In Vivo RNA Delivery and Non-Viral CRISPR/Cas Gene Editing.
Degree: 2018, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/8304
► The delivery of nucleic acids is an emerging therapeutic modality in clinical development for the treatment of many genetic diseases. The use of RNA interference…
(more)
▼ The delivery of nucleic acids is an emerging therapeutic modality in clinical development for the treatment of many genetic diseases. The use of
RNA interference (RNAi) as a therapeutic is an exciting and rapidly developing field that offers a promising alternative to small molecule drugs for the treatment of dysregulatory diseases, including cancer. Small interfering
RNA (siRNA) can be designed against any mRNA target, and upon loading into the
RNA-induced silencing complex (RISC) can enable sequence-specific target recognition and degradation. Meanwhile,
messenger RNA is currently being utilized for protein replacement therapy and for the development of vaccines by expressing viral antigens on dendritic cells. However, because
RNA molecules are unable to passively diffuse across plasma membranes due to a high molecular weight (~13 kDa for siRNA, >300 kDa for mRNA), hydrophilicity and strong anionic charge, while also being unstable and highly immunogenic when injected systemically, nucleic acid therapeutics require carriers for effective delivery. To date, many successful carriers have been designed using amphiphilic lipid-like compounds containing amine-rich cores, but the challenges of efficient endosomal release and delivery to organs outside of the liver remain major hurdles in the field of
RNA therapeutics.
This dissertation reports the design, synthesis and characterization of two new classes of lipids with unique chemical structures and in vivo
RNA delivery capabilities to the lung: zwitterionic amino lipids (ZALs) and cationic sulfonamide amino lipids (CSALs). ZALs contain an amine rich core, hydrophobic tails introduced via conjugate addition or epoxide opening, and a zwitterionic sulfobetaine head group. ZALs were designed with a combination of cationic and zwitterionic lipid properties, to help stabilize and effectively deliver long
RNA molecules. A lead compound, ZA3-Ep10, was effective for in vivo
messenger RNA delivery and the first reported demonstration of in vivo non-viral gene editing by delivering mRNA components encoding the CRISPR/Cas gene editing platform. CSALs contain a unique chemical scaffold containing an internal quaternary ammonium group and a sulfonamide linker. A rational investigation of structure-activity relationships revealed that CSALs containing an acetate sidearm, a dimethyl amino head group and higher hydrophobic content were effective in delivery siRNA to human cancer cells in vitro. CSALs also demonstrated lung localization upon systemic delivery in vivo while also demonstrating the ability to redirect liver targeting ionizable lipid nanoparticles to the lung. These new classes of materials demonstrate the importance of structural consideration in material design for the development of nucleic acid therapeutics, while also providing structural templates for developing carriers for effective delivery to tissues outside of the liver.
Advisors/Committee Members: Ready, Joseph M., Gao, Jinming, Tambar, Uttam, Siegwart, Daniel J..
Subjects/Keywords: CRISPR-Cas Systems; Gene Editing; Gene Transfer Techniques; Nanoparticles; RNA, Guide; RNA, Messenger
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Miller, J. B. (2018). The Design, Synthesis, and Evaluation of Zwitterionic and Cationic Lipids for In Vivo RNA Delivery and Non-Viral CRISPR/Cas Gene Editing. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/8304
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Miller, Jason Brian. “The Design, Synthesis, and Evaluation of Zwitterionic and Cationic Lipids for In Vivo RNA Delivery and Non-Viral CRISPR/Cas Gene Editing.” 2018. Thesis, University of Texas Southwestern Medical Center. Accessed February 27, 2021.
http://hdl.handle.net/2152.5/8304.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Miller, Jason Brian. “The Design, Synthesis, and Evaluation of Zwitterionic and Cationic Lipids for In Vivo RNA Delivery and Non-Viral CRISPR/Cas Gene Editing.” 2018. Web. 27 Feb 2021.
Vancouver:
Miller JB. The Design, Synthesis, and Evaluation of Zwitterionic and Cationic Lipids for In Vivo RNA Delivery and Non-Viral CRISPR/Cas Gene Editing. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2018. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/2152.5/8304.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Miller JB. The Design, Synthesis, and Evaluation of Zwitterionic and Cationic Lipids for In Vivo RNA Delivery and Non-Viral CRISPR/Cas Gene Editing. [Thesis]. University of Texas Southwestern Medical Center; 2018. Available from: http://hdl.handle.net/2152.5/8304
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Michigan State University
30.
Kutas, Susan Michele.
Characterization of ribonucleoprotein complexes assembled on pre-edited messenger RNAs in Trypanosoma brucei.
Degree: MS, Department of Microbiology, 1995, Michigan State University
URL: http://etd.lib.msu.edu/islandora/object/etd:25549
Subjects/Keywords: Trypanosoma brucei; RNA editing; Messenger RNA
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kutas, S. M. (1995). Characterization of ribonucleoprotein complexes assembled on pre-edited messenger RNAs in Trypanosoma brucei. (Masters Thesis). Michigan State University. Retrieved from http://etd.lib.msu.edu/islandora/object/etd:25549
Chicago Manual of Style (16th Edition):
Kutas, Susan Michele. “Characterization of ribonucleoprotein complexes assembled on pre-edited messenger RNAs in Trypanosoma brucei.” 1995. Masters Thesis, Michigan State University. Accessed February 27, 2021.
http://etd.lib.msu.edu/islandora/object/etd:25549.
MLA Handbook (7th Edition):
Kutas, Susan Michele. “Characterization of ribonucleoprotein complexes assembled on pre-edited messenger RNAs in Trypanosoma brucei.” 1995. Web. 27 Feb 2021.
Vancouver:
Kutas SM. Characterization of ribonucleoprotein complexes assembled on pre-edited messenger RNAs in Trypanosoma brucei. [Internet] [Masters thesis]. Michigan State University; 1995. [cited 2021 Feb 27].
Available from: http://etd.lib.msu.edu/islandora/object/etd:25549.
Council of Science Editors:
Kutas SM. Characterization of ribonucleoprotein complexes assembled on pre-edited messenger RNAs in Trypanosoma brucei. [Masters Thesis]. Michigan State University; 1995. Available from: http://etd.lib.msu.edu/islandora/object/etd:25549
◁ [1] [2] [3] [4] [5] … [15] ▶
.