subject:(Polyadenylation)

Miami University

1. Guo, Cheng. GENOME WIDE ANALYSES OF ALTERNATIVE POLYADENYLATION IN ARABIDOPSIS.

Degree: PhD, Cell, Molecular and Structural Biology (CMSB), 2016, Miami University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=miami1479081485753738

► This dissertation was initiated to investigate the potential association between DNA methylation and alternative polyadenylation (APA) in Arabidopsis. Through the course of research, other topics… (more)

▼ This dissertation was initiated to investigate the potential association between DNA methylation and alternative polyadenylation (APA) in Arabidopsis. Through the course of research, other topics derived from this initial study emerged with different perspectives. These four chapters were separately documented in Chapters 2, 3, 4 and 5. In addition, Chapters 1 and 6 provide the overview of introduction and conclusions to the dissertation, respectively. Chapter 2 is focused on studying the association between APA and DNA methylation in Arabidopsis. By analyzing and comparing the poly(A) tag sequencing (PAT-seq) data from met1-3 mutants with their control plants, we observed a global negative correlation between the abundance of DNA methylation and APA, and identified a number of poly(A) clusters (PACs) and genes, whose expression have been affected, which may caused by the loss of CG DNA methylation in the met1-3 mutant. In Chapter 3, we detected and characterized more than 11000 non-3UTR polyadenylation sites (n3PASs) clusters in Arabidopsis genome. Further analyses suggested that the occurrence of these n3PASs were positively correlated with certain characteristics of their respective host genes and surrounding genetic context. In Chapter 4, we conducted a genome wide comparative analysis by characterizing and comparing miniature inverted repeat transposable elements (MITEs) in 19 Arabidopsis thaliana accessions. After acquiring the positional information, we further looked into their potential impacts on genome, regarding the formation of new polyadenylation site and gene expression regulation. In Chapter 5 (a side project), we looked into the expression profiles of siRNAs and miRNAs before and after viral infection in both wild type and transgenic viral resistant rice plants with small RNA high-throughput sequencing data. We confirmed that the newly generated siRNAs, which is the major contributor of the viral resistance, were derived from the engineered inverted repeat construct, and summarized the interplay between siRNAs and miRNAs. Advisors/Committee Members: Chun, Liang (Advisor).

Subjects/Keywords: Bioinformatics; Alternative polyadenylation; Arabidopsis; DNA methylation; non3UTR polyadenylation; MITEs

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APA (6^th Edition):

Guo, C. (2016). GENOME WIDE ANALYSES OF ALTERNATIVE POLYADENYLATION IN ARABIDOPSIS. (Doctoral Dissertation). Miami University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=miami1479081485753738

Chicago Manual of Style (16^th Edition):

Guo, Cheng. “GENOME WIDE ANALYSES OF ALTERNATIVE POLYADENYLATION IN ARABIDOPSIS.” 2016. Doctoral Dissertation, Miami University. Accessed March 07, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=miami1479081485753738.

MLA Handbook (7^th Edition):

Guo, Cheng. “GENOME WIDE ANALYSES OF ALTERNATIVE POLYADENYLATION IN ARABIDOPSIS.” 2016. Web. 07 Mar 2021.

Vancouver:

Guo C. GENOME WIDE ANALYSES OF ALTERNATIVE POLYADENYLATION IN ARABIDOPSIS. [Internet] [Doctoral dissertation]. Miami University; 2016. [cited 2021 Mar 07]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=miami1479081485753738.

Council of Science Editors:

Guo C. GENOME WIDE ANALYSES OF ALTERNATIVE POLYADENYLATION IN ARABIDOPSIS. [Doctoral Dissertation]. Miami University; 2016. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=miami1479081485753738

University of California – Irvine

2. Chan, Serena Leong. Characterization of the Mammalian mRNA 3' Processing Complex.

Degree: Biomedical Sciences, 2014, University of California – Irvine

URL: http://www.escholarship.org/uc/item/0m16c8r4

► mRNA 3' processing, which typically involves an endonucleoytic cleavage followed by polyadenylation (addition of a string of adenosines), is an essential step in eukaryotic gene… (more)

▼ mRNA 3' processing, which typically involves an endonucleoytic cleavage followed by polyadenylation (addition of a string of adenosines), is an essential step in eukaryotic gene expression and significantly impacts many other gene expression steps such as transcription, splicing, mRNA export and translation (Zhao et al. 1999) (Chan et al. 2010) (Colgan et al. 1997) (Moore et al. 2009). Additionally, 3' processing is needed for gene regulation. Recent studies revealed that approximately 70% of human genes produce multiple mRNA isoforms with different 3' processing sites (Derti et al. 2012) (Hoque et al. 2013). These mRNA isoforms may encode different proteins or produce different 3' untranslated regions. This phenomenon, called alternative polyadenylation (APA), significantly expands the coding capacity of the genome and has been increasingly recognized as a critical mechanism for eukaryotic gene regulation (Di Giammartino et al. 2011) (Shi 2012) (Proudfoot 2011) (Tian et al. 2013). In addition, aberrant mRNA 3' processing causes a wide range of diseases, including IPEX syndrome, thalassemia and has been implicated in the development of cancer (Danckwardt et al. 2008) (Mayr et al. 2009). Therefore, it is critical to understand both the mechanism of mRNA 3' processing and its regulation. mRNA 3' processing requires specific RNA-protein and protein-protein interactions. The proteins required in mammals include four multi-subunit complexes and the poly (A) polymerase (PAP) while the main RNA sequences include the AAUAAA hexamer and U/G-rich elements (Zhao et al. 1999) (Chan et al. 2010) (Colgan et al. 1997). A central question in the mRNA 3' processing field has been to understand how the mRNA 3' processing sites, also called poly (A) sites, are specifically recognized and regulated. To shed light on this important question, I carried out three projects. First, comprehensive proteomic analyses of the mRNA 3' processing machinery were performed. These were accomplished by purifying all sixteen essential mRNA 3' processing factors by immunoprecipitation and identifying their associated proteins through high throughput mass spectrometry analyses. The results of this study not only provided a nearly comprehensive interactome map of the mRNA 3' processing machinery, but also revealed potential new regulatory mechanisms. I have experimentally validated the association between the mRNA 3' processing factors and some of the newly identified interacting proteins, including several ubiquitin E3 ligases, and have provided evidence that these factors regulate the stabilities of mRNA 3' processing factors. Second, I have characterized the mechanism by which the cleavage and polyadenylation specificity factor (CPSF) specifically recognizes the AAUAAA hexamer. In contrast to the prevalent model in which the CPSF subunit, CPSF 160, recognizes the AAUAAA by itself, my data provided direct evidence that the CPSF subunits, CPSF 30 and WDR33, directly bind to AAUAAA together. Additionally, I showed that the CPSF 30-RNA interaction is…

Subjects/Keywords: Biology; mRNA 3' Processing; polyadenylation; RNA

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APA (6^th Edition):

Chan, S. L. (2014). Characterization of the Mammalian mRNA 3' Processing Complex. (Thesis). University of California – Irvine. Retrieved from http://www.escholarship.org/uc/item/0m16c8r4

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Chan, Serena Leong. “Characterization of the Mammalian mRNA 3' Processing Complex.” 2014. Thesis, University of California – Irvine. Accessed March 07, 2021. http://www.escholarship.org/uc/item/0m16c8r4.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Chan, Serena Leong. “Characterization of the Mammalian mRNA 3' Processing Complex.” 2014. Web. 07 Mar 2021.

Vancouver:

Chan SL. Characterization of the Mammalian mRNA 3' Processing Complex. [Internet] [Thesis]. University of California – Irvine; 2014. [cited 2021 Mar 07]. Available from: http://www.escholarship.org/uc/item/0m16c8r4.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chan SL. Characterization of the Mammalian mRNA 3' Processing Complex. [Thesis]. University of California – Irvine; 2014. Available from: http://www.escholarship.org/uc/item/0m16c8r4

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Boston University

3. Hayward, Oliver James. Mechanisms of Mononegavirales gene expression.

Degree: MS, Medical Sciences, 2019, Boston University

URL: http://hdl.handle.net/2144/38661

► The Mononegavirales order unifies the non-segmented negative sense viruses (nsNSVs), including Marburgvirus (MARV) of the Filoviridae family and respiratory syncytial virus (RSV) of the Pneumoviridae.… (more)

▼ The Mononegavirales order unifies the non-segmented negative sense viruses (nsNSVs), including Marburgvirus (MARV) of the Filoviridae family and respiratory syncytial virus (RSV) of the Pneumoviridae. The mechanism of action of these viruses and how they infect cells are very similar, especially when focusing on their polymerases, which are distinct from those of eukaryotes and therefore possible targets for antiviral drugs. nsNSVs utilize a RNA-dependent RNA polymerase to either replicate the viral RNA genome or transcribe it into positive sense mRNA. Despite this, these two viruses result in very different, but equally devastating, effects in humans. Whereas MARV virus often results in rare but fatal hemorrhagic fevers, RSV is a common seasonal virus that can result in long term negative effects to respiratory health. These negative effects on public health demand extensive research in these two fields and a need to develop new technology and methods in order to uncover the missing pieces of viral gene expression. Specifically, the development of a MARV minigenome system would allow for increased testing of this virus outside of the confines of the biosafety level 4 (BSL-4) setting. By replacing MARV genes with reporter genes, but retaining the characteristic leader, intergenic, and trailer regions of the genome, tests involving site directed mutagenesis would reveal new insights into the crucial genomic elements needed for successful gene expression. Coupled with the transfection of the minigenome with plasmids coding for the crucial MARV proteins, artificial changes to the genome would lead to the presence of absence of translated bioluminescent reporter proteins. Using these two viruses, this study attempted to find commonalities across families. Specifically, the goals of this research were twofold, to find the optimal ratio of MARV plasmids in the minigenome system to understand the effects of the stem-loop secondary structure of MARV mRNA transcripts as well as determine the tail length of the poly(A) tail of RSV mRNA transcripts using digestion and probing primers. Calculating the RSV poly(A) tail length would allow for further research into determining whether the MARV and RSV polymerase polyadenylates before or after it releases the transcript. Despite multiple failed attempts, transfections using pCAGGS plasmids and the eGFP monocistronic minigenome in a 6-well plate qualitatively demonstrated the need for pCAGGS-L plasmid concentration of 1000 ng/µl. Due to time constraints, the poly(A) tail length of the RSV NS-1 mRNA transcript could not be determined. Overall, this study focused on gaining new insights on the techniques and procedures necessary for conducting virus research in a biosafety level 2 (BSL-2) setting, as well as developing troubleshooting skills in approaching fail experiments. Advisors/Committee Members: Fearns, Rachel (advisor), Muhlberger, Elke (advisor).

Subjects/Keywords: Medicine; Marburg; Minigenome; Polyadenylation; Respiratory; Syncytial; Transfection

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hayward, O. J. (2019). Mechanisms of Mononegavirales gene expression. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/38661

Chicago Manual of Style (16^th Edition):

Hayward, Oliver James. “Mechanisms of Mononegavirales gene expression.” 2019. Masters Thesis, Boston University. Accessed March 07, 2021. http://hdl.handle.net/2144/38661.

MLA Handbook (7^th Edition):

Hayward, Oliver James. “Mechanisms of Mononegavirales gene expression.” 2019. Web. 07 Mar 2021.

Vancouver:

Hayward OJ. Mechanisms of Mononegavirales gene expression. [Internet] [Masters thesis]. Boston University; 2019. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/2144/38661.

Council of Science Editors:

Hayward OJ. Mechanisms of Mononegavirales gene expression. [Masters Thesis]. Boston University; 2019. Available from: http://hdl.handle.net/2144/38661

Texas Tech University

4. McMahon, K. Wyatt. Multiple mechanisms of polyadenylation site choice in male germ cells.

Degree: TTUHSC – Molecular Cell Biology and Biotechnology, 2007, Texas Tech University

URL: http://hdl.handle.net/2346/15955

► Polyadenylation, the process involved in the formation of the poly(A) tail at the 3¡¬ end of eukaryotic messenger RNAs (mRNAs), has been traditionally described as… (more)

Subjects/Keywords: Polyadenylation; mRNA processing

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

McMahon, K. W. (2007). Multiple mechanisms of polyadenylation site choice in male germ cells. (Thesis). Texas Tech University. Retrieved from http://hdl.handle.net/2346/15955

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

McMahon, K Wyatt. “Multiple mechanisms of polyadenylation site choice in male germ cells.” 2007. Thesis, Texas Tech University. Accessed March 07, 2021. http://hdl.handle.net/2346/15955.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

McMahon, K Wyatt. “Multiple mechanisms of polyadenylation site choice in male germ cells.” 2007. Web. 07 Mar 2021.

Vancouver:

McMahon KW. Multiple mechanisms of polyadenylation site choice in male germ cells. [Internet] [Thesis]. Texas Tech University; 2007. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/2346/15955.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

McMahon KW. Multiple mechanisms of polyadenylation site choice in male germ cells. [Thesis]. Texas Tech University; 2007. Available from: http://hdl.handle.net/2346/15955

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

5. Sheppard, Sarah E. Application of a Naïve Bayes Classifier to Assign Polyadenylation Sites from 3' End Deep Sequencing Data: A Dissertation.

Degree: PhD, Molecular, Cell and Cancer Biology Department, 2013, U of Massachusetts : Med

URL: http://escholarship.umassmed.edu/gsbs_diss/653

► Cleavage and polyadenylation of a precursor mRNA is important for transcription termination, mRNA stability, and regulation of gene expression. This process is directed by… (more)

Subjects/Keywords: Bayes Theorem; Algorithms; Polyadenylation; RNA 3' Polyadenylation Signals; High-Throughput Nucleotide Sequencing; Bioinformatics; Computational Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sheppard, S. E. (2013). Application of a Naïve Bayes Classifier to Assign Polyadenylation Sites from 3' End Deep Sequencing Data: A Dissertation. (Doctoral Dissertation). U of Massachusetts : Med. Retrieved from http://escholarship.umassmed.edu/gsbs_diss/653

Chicago Manual of Style (16^th Edition):

Sheppard, Sarah E. “Application of a Naïve Bayes Classifier to Assign Polyadenylation Sites from 3' End Deep Sequencing Data: A Dissertation.” 2013. Doctoral Dissertation, U of Massachusetts : Med. Accessed March 07, 2021. http://escholarship.umassmed.edu/gsbs_diss/653.

MLA Handbook (7^th Edition):

Sheppard, Sarah E. “Application of a Naïve Bayes Classifier to Assign Polyadenylation Sites from 3' End Deep Sequencing Data: A Dissertation.” 2013. Web. 07 Mar 2021.

Vancouver:

Sheppard SE. Application of a Naïve Bayes Classifier to Assign Polyadenylation Sites from 3' End Deep Sequencing Data: A Dissertation. [Internet] [Doctoral dissertation]. U of Massachusetts : Med; 2013. [cited 2021 Mar 07]. Available from: http://escholarship.umassmed.edu/gsbs_diss/653.

Council of Science Editors:

Sheppard SE. Application of a Naïve Bayes Classifier to Assign Polyadenylation Sites from 3' End Deep Sequencing Data: A Dissertation. [Doctoral Dissertation]. U of Massachusetts : Med; 2013. Available from: http://escholarship.umassmed.edu/gsbs_diss/653

University of Louisville

6. Wang, Xiangping. The expression and localization of cytoplasmic polyadenylation element binding proteins in the retina.

Degree: PhD, 2008, University of Louisville

URL: 10.18297/etd/1510 ; https://ir.library.louisville.edu/etd/1510

► The current status of our knowledge of synaptic plasticity comes largely from studies of the hippocampus and the context of learning and memory. We remain… (more)

▼ The current status of our knowledge of synaptic plasticity comes largely from studies of the hippocampus and the context of learning and memory. We remain largely ignorant of plasticity in other neural systems and contexts. The molecular basis of plasticity has recently been given new impetus due to the discovery of a local control mechanism which can regulate protein synthesis at stimulated synapses. This involves the use of cytoplasmic polyadenylation binding proteins (CPEBs) to regulate translation. The studies presented here attempt to show that these molecular components are present in the retina, a part of the central nervous system that has been seen, historically, as not plastic. Methods used. RT-PCR was used to determine the presence of mRNAs in tissue. In situ hybridization and immunofluorescence microscopy were used for localization of mRNAs and proteins respectively. Real-time PCR and Western blots were used for quantifications of mRNA and proteins during postnatal development. A bioinformatics program "CPE detector" and 3' RACE were used to identify potential mRNA targets for CPEB1 in the UTR databases and in the retina respectively. The PAT assay was used to determine the length of poly(A) tails for some potential mRNA targets. Data mining and sequence alignment were used to identify alternatively spliced isoforms of CPEB3. Major results. Our results demonstrated that CPEB1-4 were all present in the retina. The four CPEBs had similar distributions in the inner retina: predominantly in the retinal ganglion cell layer, and to a less extent, in the inner nuclear layer. However, CPEB1 had a laminar pattern in the inner plexiform layer, whereas CPEB3 was diffuse. The presence of CPEB1 was minimal in the outer plexiform layer in contrast to CPEB3. During postnatal development the levels of CPEB1, 3 and 4 were up-regulated; whereas the level of CPEB2 was constant. Potential mRNAs were identified as targets of CPEB1; some mRNA targets demonstrated elongated poly(A) tails at postnatal day7 or day12, consistent with the up-regulation of CPEB1 at these ages. Multiple isoforms, including a novel one, were identified for CPEB3. The alternative splicing of CPEB3 could occur both in the UTRs and in the coding region. Major conclusions/significance. Our data demonstrated that more than one CPEB paralog is present in mouse retina. Potential mRNA targets for CPEB1 were present in the retina and gained elongated poly(A) tail in accordance with the up-regulation of CPEB1 during development. The increases of CPEB1, 3 and 4 during the development indicate a possible role of such CPEBs in synaptogenesis. Continuing up-regulation of CPEB1, 3 and 4 also indicate a role in the adult retina. Alternative splicing in the UTRs of CPEB3 indicates a complex regulation of CPEB3; multiple isoforms of CPEB3 protein indicate the functional complexity of CPEB3. The presence of CPEBs in the retina indicates the existence of a translational control system in the retina. Future studies. Future studies should focus on the identification of… Advisors/Committee Members: Cooper, Nigel G. F..

Subjects/Keywords: Polyadenylation; CPEBs; Cytoplasmic polyadenylation; Alternative splicing

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wang, X. (2008). The expression and localization of cytoplasmic polyadenylation element binding proteins in the retina. (Doctoral Dissertation). University of Louisville. Retrieved from 10.18297/etd/1510 ; https://ir.library.louisville.edu/etd/1510

Chicago Manual of Style (16^th Edition):

Wang, Xiangping. “The expression and localization of cytoplasmic polyadenylation element binding proteins in the retina.” 2008. Doctoral Dissertation, University of Louisville. Accessed March 07, 2021. 10.18297/etd/1510 ; https://ir.library.louisville.edu/etd/1510.

MLA Handbook (7^th Edition):

Wang, Xiangping. “The expression and localization of cytoplasmic polyadenylation element binding proteins in the retina.” 2008. Web. 07 Mar 2021.

Vancouver:

Wang X. The expression and localization of cytoplasmic polyadenylation element binding proteins in the retina. [Internet] [Doctoral dissertation]. University of Louisville; 2008. [cited 2021 Mar 07]. Available from: 10.18297/etd/1510 ; https://ir.library.louisville.edu/etd/1510.

Council of Science Editors:

Wang X. The expression and localization of cytoplasmic polyadenylation element binding proteins in the retina. [Doctoral Dissertation]. University of Louisville; 2008. Available from: 10.18297/etd/1510 ; https://ir.library.louisville.edu/etd/1510

7. Oruganty, Aparna. Role of the Cytoplasmic Polyadenylation Element Binding Proteins in Neuron: A Dissertation.

Degree: Interdisciplinary Graduate Program, Program in Molecular Medicine, 2013, U of Massachusetts : Med

URL: http://escholarship.umassmed.edu/gsbs_diss/648

► Genome regulation is an extremely complex phenomenon. There are various mechanisms in place to ensure smooth performance of the organism. Post-transcriptional regulation of gene… (more)

Subjects/Keywords: Polyadenylation; RNA-Binding Proteins; Transcription Factors; mRNA Cleavage and Polyadenylation Factors; Neurons; Cell and Developmental Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Oruganty, A. (2013). Role of the Cytoplasmic Polyadenylation Element Binding Proteins in Neuron: A Dissertation. (Doctoral Dissertation). U of Massachusetts : Med. Retrieved from http://escholarship.umassmed.edu/gsbs_diss/648

Chicago Manual of Style (16^th Edition):

Oruganty, Aparna. “Role of the Cytoplasmic Polyadenylation Element Binding Proteins in Neuron: A Dissertation.” 2013. Doctoral Dissertation, U of Massachusetts : Med. Accessed March 07, 2021. http://escholarship.umassmed.edu/gsbs_diss/648.

MLA Handbook (7^th Edition):

Oruganty, Aparna. “Role of the Cytoplasmic Polyadenylation Element Binding Proteins in Neuron: A Dissertation.” 2013. Web. 07 Mar 2021.

Vancouver:

Oruganty A. Role of the Cytoplasmic Polyadenylation Element Binding Proteins in Neuron: A Dissertation. [Internet] [Doctoral dissertation]. U of Massachusetts : Med; 2013. [cited 2021 Mar 07]. Available from: http://escholarship.umassmed.edu/gsbs_diss/648.

Council of Science Editors:

Oruganty A. Role of the Cytoplasmic Polyadenylation Element Binding Proteins in Neuron: A Dissertation. [Doctoral Dissertation]. U of Massachusetts : Med; 2013. Available from: http://escholarship.umassmed.edu/gsbs_diss/648

University of Florida

8. Manchanda, Mini. Dysregulation of Distinct RNA Processing Steps in Myotonic Dystrophy.

Degree: PhD, Medical Sciences - Genetics (IDP), 2014, University of Florida

URL: https://ufdc.ufl.edu/UFE0046638

► Many RNA-binding proteins (RBPs) regulate multiple steps in mRNA metabolism from transcription and maturation in the nucleus to localization, translation and decay in the cytoplasm.… (more)

▼ Many RNA-binding proteins (RBPs) regulate multiple steps in mRNA metabolism from transcription and maturation in the nucleus to localization, translation and decay in the cytoplasm. Tissue specific RNA binding proteins are key players that extensively regulate pre-mRNA processing, mRNA localization, translation and turnover to achieve the precise spatial and temporal expression of specific transcripts that is essential for maintaining cellular homeostasis. Often RBP family members regulate different aspects of mRNA metabolism, however the mechanism of coordinate regulation of specific steps by individual RBPs is unclear. Muscleblind-like proteins are alternative splicing factors expressed in a tissue and developmental stage specific manner and loss of their functions manifests into the multi-systemic disease, myotonic dystrophy (dystrophia myotonica, DM). In this study, we used advanced biochemical procedures and transcriptome wide high-throughput sequencing approaches to determine that, in addition to their roles in alternative RNA splicing, Mbnl proteins function as alternative polyadenylation factors through direct binding to cis-regulatory elements in the three prime untranslated regions (UTRs) of their RNA targets. Furthermore, we show that Mbnl1 and Mbn2 are functionally redundant irrespective of their spatial expression differences in vivo. These proteins bind to the similar (Y/R)GCY motifs in their mRNA targets and have similar binding distributions throughout the genome. Although alternative splicing (AS) of target mRNAs are maintained following the loss of single Mbnl paralogs, combined loss of Mbnl1 and Mbnl2 lead to widespread AS changes. These results suggest functional compensation among Mbnl paralogs. Moreover, integration of the splicing and polyadenylation data showed that the role of Mbnl proteins in alternative polyadenylation is largely independent of their splicing roles. While Mbnl proteins regulate AS and APA of distinct RNA targets, these binding targets are functionally linked and involved in common cellular pathways controlling cell proliferation and cytoskeletal organization in mouse embryonic fibroblast (MEFs). We conclude that the Mbnl proteins are multi-functional and coordinately regulate the co/post transcriptional processing of diverse, yet functionally linked RNAs. This study also provides experimental evidence that DM is an RNA processing, and not simply an AS, disorder. A systems biology approach is warranted to understand the multiple pathways that are impacted in DM, which should have a significant impact on the development of effective treatments for this hereditary disease. ( en ) Advisors/Committee Members: SWANSON,MAURICE S (committee chair), CONDIT,RICHARD C (committee member), RENNE,ROLF FRIEDRICH (committee member), FLANEGAN,JAMES B (committee member).

Subjects/Keywords: Alternative splicing; Cells; Exons; Genes; Genomes; Messenger RNA; Polyadenylation; Protein isoforms; RNA; Splicing; mbnl – polyadenylation – rna – splicing

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Manchanda, M. (2014). Dysregulation of Distinct RNA Processing Steps in Myotonic Dystrophy. (Doctoral Dissertation). University of Florida. Retrieved from https://ufdc.ufl.edu/UFE0046638

Chicago Manual of Style (16^th Edition):

Manchanda, Mini. “Dysregulation of Distinct RNA Processing Steps in Myotonic Dystrophy.” 2014. Doctoral Dissertation, University of Florida. Accessed March 07, 2021. https://ufdc.ufl.edu/UFE0046638.

MLA Handbook (7^th Edition):

Manchanda, Mini. “Dysregulation of Distinct RNA Processing Steps in Myotonic Dystrophy.” 2014. Web. 07 Mar 2021.

Vancouver:

Manchanda M. Dysregulation of Distinct RNA Processing Steps in Myotonic Dystrophy. [Internet] [Doctoral dissertation]. University of Florida; 2014. [cited 2021 Mar 07]. Available from: https://ufdc.ufl.edu/UFE0046638.

Council of Science Editors:

Manchanda M. Dysregulation of Distinct RNA Processing Steps in Myotonic Dystrophy. [Doctoral Dissertation]. University of Florida; 2014. Available from: https://ufdc.ufl.edu/UFE0046638

University of California – Irvine

9. Weng, Lingjie. Computational Approaches Toward a Polyadenylation Code.

Degree: Computer Science, 2014, University of California – Irvine

URL: http://www.escholarship.org/uc/item/9118p3bc

► Messenger RNA 3' polyadenylation (poly(A)) is an essential post-transcriptional processing step for most eukaryotic genes, significantly impacting many aspects of mRNA metabolism. The majority of… (more)

▼ Messenger RNA 3' polyadenylation (poly(A)) is an essential post-transcriptional processing step for most eukaryotic genes, significantly impacting many aspects of mRNA metabolism. The majority of eukaryotic genes present alternative poly(A) (APA), through which the same gene can have multiple alternative 3' ends due to the cleavage and poly(A) presence at distinct sites. APA results in RNA transcripts with different 3'UTRs, which can influence transcript transport, localization, stability, and translation, or lead to different protein products. Many human diseases including cancer have been associated with abnormal poly(A) regulation, highlighting the importance of this process. However, the rules on how poly(A) sites are selected and regulated – the so called the poly(A) code – are not well understood.Recent advances in high-throughput technologies have provided a great opportunity to elucidate the rules underlying APA. High-throughput sequencing(HTS) experiments yield a wealth of data regarding APA. Consequently, there is a need to develop computational techniques to mine these data. In this thesis, we present four major contributions furthering our understanding of the poly(A) code. The algorithms and computational methods we developed have all showed improved predictive and analytical capabilities over competing methods. They are as follows:1) HTS reads need to be efficiently mapped back to a reference genome for further downstream analysis. To address this need, we developed a fast and accurate reads mapping package for identifying all mapping locations for each read, called "Hobbes". Hobbes outperforms most state-of-the-art "all-mapping" programs, including mrsFast and Razers2.2) We developed a bioinformatics pipeline for identifying and profiling genes with significant APA switches from different biological or clinical conditions. The pipeline includes calling poly(A) sites, filtering artificial poly(A) sites, clustering heterogeneous poly(A) sites, and identifying and profiling genes with significant APA switches. This pipeline has already provided significant insights into many core polyadenylation factors.3) The poly(A) code can be partially deciphered from the genome-wide modeling of tissue-specific APA. Consequently, extended existing Shannon entropy measuring to assess the tissue specificity for each poly(A) site, and applied an outlier detection method to identifying the tissue-specific pattern. With new mRNA features we explored, our ensemble predictive model successfully discriminated tissue-specific poly(A) sites from constitutive poly(A) sites, with test accuracy 84.5% (auRoc 0.92), which surpassed the previous model by more than 10%. Through an in-depth analysis of the most important features, we proposed a mechanism that controls the selection and regulation of tissue-specific APA. 4) Aberrant mRNA 3' polyadenylation have been implicated for a wide variety of complex diseases. We developed a novel statistical method for identifying disease-related pathway from genome-wide association studies…

Subjects/Keywords: Bioinformatics; Computer science; Computational Biology; High-throughput Data; Machine Learning; Polyadenylation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Weng, L. (2014). Computational Approaches Toward a Polyadenylation Code. (Thesis). University of California – Irvine. Retrieved from http://www.escholarship.org/uc/item/9118p3bc

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Weng, Lingjie. “Computational Approaches Toward a Polyadenylation Code.” 2014. Thesis, University of California – Irvine. Accessed March 07, 2021. http://www.escholarship.org/uc/item/9118p3bc.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Weng, Lingjie. “Computational Approaches Toward a Polyadenylation Code.” 2014. Web. 07 Mar 2021.

Vancouver:

Weng L. Computational Approaches Toward a Polyadenylation Code. [Internet] [Thesis]. University of California – Irvine; 2014. [cited 2021 Mar 07]. Available from: http://www.escholarship.org/uc/item/9118p3bc.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Weng L. Computational Approaches Toward a Polyadenylation Code. [Thesis]. University of California – Irvine; 2014. Available from: http://www.escholarship.org/uc/item/9118p3bc

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidade Federal de Viçosa

10. Ramon de Freitas Santos. Padrões de poliadenilação em moléculas de RNAs de Leishmania obtidas da análise de transcriptoma.

Degree: 2012, Universidade Federal de Viçosa

URL: http://www.tede.ufv.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=5028

►

Os sequenciamentos de próxima geração (NGS) em larga escala e de alto rendimento revelaram novos aspectos nos genomas e transcriptomas que não foram observados ou… (more)

▼

Os sequenciamentos de próxima geração (NGS) em larga escala e de alto rendimento revelaram novos aspectos nos genomas e transcriptomas que não foram observados ou foram pobremente descritos usando sequenciamento em pequena escala. Usando duas espécies de Leishmania como modelo numa análise global do transcriptoma por pirosequenciamento (454/Roche) encontramos poliadenilações não canônicas em moléculas de rRNAs e mRNAs. Os RNAs em Leishmania são transcritos como longas moléculas policistrônicas pós-transcricionalmente processadas, mas usualmente somente o mRNA é poliadenilado estavelmente na sua extremidade 3- madura. Analisando os dados de transcriptoma também observamos caudas poli(A)+ ou ricas em poli(A)+ na extremidade 3 dos genes de rRNA. Este fenômeno poderia estar diretamente relacionado com uma usual contaminação por rRNAs observada de modo geral nas amostras de mRNAs após purificação por afinidade à oligo(dT). Surpreendentemente, encontramos muitas caudas poli(A)+ homo- ou heteropoliméricas na extremidade 3 e internamente localizadas nos transcritos preditos (rRNA e mRNA) interrompendo a informação e provavelmente relacionadas com um mecanismo ainda não observado de controle pós-transcricional da expressão gênica em Leishmania. Comprovamos estas observações por RT-PCR e sequenciamento convencional usando os genes ribossomais SSU 18S, LSU 28S alfa e LSU 28S beta e mensageiros eiF5a2 e proteína 60S ribossomal como alvos experimentais. O fenômeno de adição de cauda poli(A)+ em moléculas truncadas expande as fronteiras do conhecimento a respeito da regulação da expressão gênica em Leishmania e organismos relacionados e sugere a presença de um controle póstranscricional baseado no turnover de RNAs. A presença de transcritos homólogos à proteínas componentes do exossoma de outros organismos foi também observada, sugerindo que esta maquinaria seja ativa em Leishmania. A integridade das moléculas transcritas pode ter um papel importante na regulação dos genes que efetivamente são traduzidos. Estes dados destacam a importância de avaliar estas modificações pós-transcricionais nas análises globais do transcriptoma e abrem SANTOS, R. F. Resumo novos campos de pesquisa nos estudos globais de expressão gênica diferencial em tripanosomatídeos.

The high throughput next generation sequencing (NGS) has revealed new aspects on genomes and transcriptomes that was not observed or poor described using small scale sequencing. Using two species of Leishmania as a model in a typical transcriptome analysis and the NGS 454 pirosequencing we found non canonical polyadenilations at rRNAs and mRNAs. Leishmanias RNAs, including rRNAs are transcribed as polycistronical long pre-rRNAs, but usually only mRNAs are processed by poly(A)+ polymerases that add canonical 3-poly(A)+ tails. Analyzing the transcriptome data we observed poly(A)+ rich tails at the end of rRNA subunits too. This phenomenon could be direct related with the common high rRNA contaminants observed in general mRNA samples after purification by oligo(dT) affinity approach.…

Advisors/Committee Members: Luis Carlos Crocco Afonso, Luciano Gomes Fietto, Márcia Rogéria de Almeida Lamêgo, Eduardo de Almeida Marques da Silva, Cláudio Lísias Mafra de Siqueira, Gustavo Costa Bressan, Antônio Helvécio Tótola, Juliana Lopes Rangel Fietto.

Subjects/Keywords: BIOLOGIA MOLECULAR; Poliadenilação; Leismania; Transcriptoma; Polyadenylation; Leishmania; Transcriptome

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❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Santos, R. d. F. (2012). Padrões de poliadenilação em moléculas de RNAs de Leishmania obtidas da análise de transcriptoma. (Thesis). Universidade Federal de Viçosa. Retrieved from http://www.tede.ufv.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=5028

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Santos, Ramon de Freitas. “Padrões de poliadenilação em moléculas de RNAs de Leishmania obtidas da análise de transcriptoma.” 2012. Thesis, Universidade Federal de Viçosa. Accessed March 07, 2021. http://www.tede.ufv.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=5028.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Santos, Ramon de Freitas. “Padrões de poliadenilação em moléculas de RNAs de Leishmania obtidas da análise de transcriptoma.” 2012. Web. 07 Mar 2021.

Vancouver:

Santos RdF. Padrões de poliadenilação em moléculas de RNAs de Leishmania obtidas da análise de transcriptoma. [Internet] [Thesis]. Universidade Federal de Viçosa; 2012. [cited 2021 Mar 07]. Available from: http://www.tede.ufv.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=5028.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Santos RdF. Padrões de poliadenilação em moléculas de RNAs de Leishmania obtidas da análise de transcriptoma. [Thesis]. Universidade Federal de Viçosa; 2012. Available from: http://www.tede.ufv.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=5028

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Oxford

11. Hardy, Jessica. Human cleavage factor I (CFIm) and its role in alternative polyadenylation of pre-mRNA.

Degree: PhD, 2017, University of Oxford

URL: http://ora.ox.ac.uk/objects/uuid:a3ba5d10-b3fa-4ab7-9709-a0d642e21543 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740914

► For many human protein-coding genes, alternative cleavage and polyadenylation (APA) of pre-mRNA generates distinct 3' untranslated regions (3'UTRs) with differing regulatory potential. Widespread 3'UTR shortening… (more)

▼ For many human protein-coding genes, alternative cleavage and polyadenylation (APA) of pre-mRNA generates distinct 3' untranslated regions (3'UTRs) with differing regulatory potential. Widespread 3'UTR shortening via APA occurs in proliferative cell states, including cancer, where it can lead to oncogene overexpression. There has therefore been significant interest in identifying factors which influence poly(A) site choice in different physiological states. The multi-subunit human cleavage factor I complex (CFIm), a core component of the mammalian pre-mRNA cleavage machinery, has been identified as a potential master regulator of APA, as its depletion leads to widespread 3'UTR shortening. However, mechanistic understanding of how CFIm influences poly(A) site selection, and how its activity is regulated, is lacking. In this work, gene editing was used to generate cell lines with substantial, permanent depletion of the 25 kDa or 68 kDa subunits of CFIm (CFIm25 and CFIm68), which exhibited the expected 3'UTR shortening for representative transcripts. Reversal of this 3'UTR shortening by CFIm25 or CFIm68 re-expression provided the basis for a complementation assay, which allowed various aspects of CFIm25 and CFIm68 function to be investigated in vivo. The capacity of CFIm25 to recognise UGUA RNA sequences was shown to make an important contribution to poly(A) site selection transcriptome-wide, and a novel function for the C-terminal arginine/serine-rich (RS domain) of CFIm68 in poly(A) site selection was identified. The potential contribution of CFIm post-translational modification (PTM) to APA regulation was also explored. Novel acetylation sites on CFIm25 and CFIm68 were identified, as well as extensive serine phosphorylation in the CFIm68 RS domain. Complementation analysis revealed that phosphomimetic mutations in this RS domain inhibited distal poly(A) site selection, suggesting a potential role for CFIm68 phosphorylation in APA regulation. Taken together, the findings presented here provide insights into several important determinants of CFIm function, and the complementation assay developed provides a useful tool for future investigations.

Subjects/Keywords: 572.8; Messenger RNA; mRNA; alternative polyadenylation; cleavage factor

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hardy, J. (2017). Human cleavage factor I (CFIm) and its role in alternative polyadenylation of pre-mRNA. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:a3ba5d10-b3fa-4ab7-9709-a0d642e21543 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740914

Chicago Manual of Style (16^th Edition):

Hardy, Jessica. “Human cleavage factor I (CFIm) and its role in alternative polyadenylation of pre-mRNA.” 2017. Doctoral Dissertation, University of Oxford. Accessed March 07, 2021. http://ora.ox.ac.uk/objects/uuid:a3ba5d10-b3fa-4ab7-9709-a0d642e21543 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740914.

MLA Handbook (7^th Edition):

Hardy, Jessica. “Human cleavage factor I (CFIm) and its role in alternative polyadenylation of pre-mRNA.” 2017. Web. 07 Mar 2021.

Vancouver:

Hardy J. Human cleavage factor I (CFIm) and its role in alternative polyadenylation of pre-mRNA. [Internet] [Doctoral dissertation]. University of Oxford; 2017. [cited 2021 Mar 07]. Available from: http://ora.ox.ac.uk/objects/uuid:a3ba5d10-b3fa-4ab7-9709-a0d642e21543 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740914.

Council of Science Editors:

Hardy J. Human cleavage factor I (CFIm) and its role in alternative polyadenylation of pre-mRNA. [Doctoral Dissertation]. University of Oxford; 2017. Available from: http://ora.ox.ac.uk/objects/uuid:a3ba5d10-b3fa-4ab7-9709-a0d642e21543 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740914

University of Colorado

12. Garrido-Lecca, Alfonso. mRNA 3' end Formation and RNA Polymerase II Termination in Caenorhabditis elegans Operons.

Degree: PhD, 2012, University of Colorado

URL: https://scholar.colorado.edu/mcdb_gradetds/12

► In most organisms, 3' end formation of the pre-mRNA and transcription termination are tightly coupled, making it impossible to study these two processes independently… (more)

▼ In most organisms, 3' end formation of the pre-mRNA and transcription termination are tightly coupled, making it impossible to study these two processes independently from each other. C. elegans, however, contains polycistronic transcripts (operons) that naturally separate 3' end processing from transcription termination, allowing me to ask questions that cannot be answered in other systems. I have used ChIP experiments in operons to study 3' end formation and transcription termination in a unique context. I found that within operons Ser-5 and Ser-2 phosphorylation of RNAPII CTD colocalized with the expected sites of pre-mRNA processing; Ser-5p was associated with sites of co-transcriptional capping, while Ser-2p was associated with 3' end formation sites. Moreover, I globally mapped the CstF-64 localization of all genes in the worm genome. I found that CstF-64 binds all 3' ends of genes, even those in which termination does not occur. Interestingly, CstF-64 colocalized with Ser-2p at 3' ends of genes, indicating that in C. elegans the CstF trimeric complex might be recruited by Ser-2 phosphorylation. I also present evidence that RNAPII at 3' ends of internal genes in operons is paused, colocalizing with Ser-2p and CstF-64, similar to the pattern seen for terminal 3' ends. These results indicate that 3' ends marked by Ser-2p, bound by CstF-64 and containing paused RNAPII are not sufficient to cause transcription termination. Finally, I investigated the 3' end formation mechanism at the 3' end of internal genes in SL1-type operons. I found no evidence supporting a cleavage event involving trans-splicing, since SL1-type operon 3' ends are marked by Ser-2p and CstF-64, similar to the patterns seen in SL2-type operons. Moreover, SL1-type operons required CstF-50 for processing their 3' ends and recruiting CstF-64, similar to SL2-type operon 3' ends. These results are consistent with the experimental results presented by Williams et al. (1999), suggesting that 3' end formation at SL1-type operons can occur through the canonical 3' end formation machinery. Advisors/Committee Members: Joaquin Espinosa, Thomas Blumenthal, David Bentley, Min Han, Ravinder Singh.

Subjects/Keywords: SL1-type operons; SL2-type operons; cleavage; polyadenylation; Biology; Molecular Biology

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❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Garrido-Lecca, A. (2012). mRNA 3' end Formation and RNA Polymerase II Termination in Caenorhabditis elegans Operons. (Doctoral Dissertation). University of Colorado. Retrieved from https://scholar.colorado.edu/mcdb_gradetds/12

Chicago Manual of Style (16^th Edition):

Garrido-Lecca, Alfonso. “mRNA 3' end Formation and RNA Polymerase II Termination in Caenorhabditis elegans Operons.” 2012. Doctoral Dissertation, University of Colorado. Accessed March 07, 2021. https://scholar.colorado.edu/mcdb_gradetds/12.

MLA Handbook (7^th Edition):

Garrido-Lecca, Alfonso. “mRNA 3' end Formation and RNA Polymerase II Termination in Caenorhabditis elegans Operons.” 2012. Web. 07 Mar 2021.

Vancouver:

Garrido-Lecca A. mRNA 3' end Formation and RNA Polymerase II Termination in Caenorhabditis elegans Operons. [Internet] [Doctoral dissertation]. University of Colorado; 2012. [cited 2021 Mar 07]. Available from: https://scholar.colorado.edu/mcdb_gradetds/12.

Council of Science Editors:

Garrido-Lecca A. mRNA 3' end Formation and RNA Polymerase II Termination in Caenorhabditis elegans Operons. [Doctoral Dissertation]. University of Colorado; 2012. Available from: https://scholar.colorado.edu/mcdb_gradetds/12

13. Idir, Yassir. Epigenetic regulation of transcription from genes-containing heterochromatin : Régulation épigénétique de la transcription des gènes contenant de l’hétérochromatine.

Degree: Docteur es, Biologie, 2019, Université Paris-Saclay (ComUE)

URL: http://www.theses.fr/2019SACLS270

►

La maturation des ARN implique un grand nombre d’évènements post-transcriptionnels, parmi lesquels la polyadénylation qui constitue une étape clé. Chez Arabidopsis, la présence de l’hétérochromatine… (more)

▼

La maturation des ARN implique un grand nombre d’évènements post-transcriptionnels, parmi lesquels la polyadénylation qui constitue une étape clé. Chez Arabidopsis, la présence de l’hétérochromatine au niveau des introns de certains gènes peut influencer considérablement la polyadénylation de leur transcrits. INCREASED IN BONSAI METHYLATION2 (IBM2) est une protéinequi contrôle cette catégorie de gènes en reconnaissant l’hétérochromatine au niveau des introns via son domaine BOMO-ADJACENT HOMOLOGY (BAH). IBM2 se lie à l’ARNm par son motif RNA RECOGNOTION (RRM), afin d’assurer la transcription complète de ces gènes cibles en favorisant l’utilisation d’un site distal de polyadénylation. Par conséquent, en mutant IBM2, des plus transcrits courts sont synthétisés suite à une polyadénylation précoce au niveau de la régionhétérochromatique. Durant ma thèse, j’ai cherché à comprendre les mécanismes moléculaires sous-jacents de cette régulation tout en étudiant le rôle du complexe protéique IBM2. Nous avons identifié des protéines partenaires d’IBM2 déjà étudiées telle que ENHANCED DOWNY MILDEW2 (EDM2) et ASI-IMMUNOPRECIPITATED PROTEIN1 (AIPP1), ainsi qu’une nouvelle protéine interagissant physiquement avec IBM2 et d’autres protéines. La mutation du gène correspondant à cette protéine conduit à une réduction de l’expression globale des cibles d’IBM2testées, accompagnée d’un niveau réduit de transcrits longs fonctionnels. Moyennant un crible génétique des suppresseurs de la mutation ibm2, nous avons identifié plusieurs facteurs agissant en amont de la voie IBM2, notamment la protéine FLOWERING TIME CONTROL (FPA). FPA est une protéine capable de s’associer à l’ARN pour favoriser l’utilisation de sites proximaux de polyadénylation de plusieurs gènes cibles, avec parmi eux des gènes contrôlés par IBM2, ce qui suggère que la transcription complète de ces gènes dépend étroitement des actions antagonistes entre IBM2 et FPA. Nos résultats ont montré que le choix du site de polyadénylation de gènes contenant de l’hétérochromatine dépend de plusieurs protéines agissant en différents complexes ainsi que l’interconnexion avec d’autres voies.

RNA maturation implies numerous post-transcriptional modifications in whichpolyadenylation is a key step. In Arabidopsis, the heterochromatin found within introns(intronic-HC) can impact transcripts polyadenylation of host genes. INCREASED IN BONSAI METHYLATION2 (IBM2), an RNA-binding protein containing a bromo-adjacent homology (BAH) domain, interacts with intronic-HC to produce functional full-length transcripts by promoting distal polyadenylation. Loss of IBM2 function triggers short transcripts production due to premature polyadenylation from the heterochromatic region. During my thesis, I investigated the role of proteins that may belong to different sub-complexes in the regulation of intronic-HC containing genes. We identified IBM2 partners, including ENHANCED DOWNY MILDEW 2 (EDM2) and ASI-IMMUNOPRECIPITATED PROTEIN1 (AIPP1), and a novel partner that interacts directly with IBM2 and other…

Advisors/Committee Members: Bouché, Nicolas (thesis director).

Subjects/Keywords: Arabidopsis; Polyadénylation; Eléments transposables; Hétérochromatine; Arabidopsis; Polyadenylation; Transposable elements; Heterochromatin

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Idir, Y. (2019). Epigenetic regulation of transcription from genes-containing heterochromatin : Régulation épigénétique de la transcription des gènes contenant de l’hétérochromatine. (Doctoral Dissertation). Université Paris-Saclay (ComUE). Retrieved from http://www.theses.fr/2019SACLS270

Chicago Manual of Style (16^th Edition):

Idir, Yassir. “Epigenetic regulation of transcription from genes-containing heterochromatin : Régulation épigénétique de la transcription des gènes contenant de l’hétérochromatine.” 2019. Doctoral Dissertation, Université Paris-Saclay (ComUE). Accessed March 07, 2021. http://www.theses.fr/2019SACLS270.

MLA Handbook (7^th Edition):

Idir, Yassir. “Epigenetic regulation of transcription from genes-containing heterochromatin : Régulation épigénétique de la transcription des gènes contenant de l’hétérochromatine.” 2019. Web. 07 Mar 2021.

Vancouver:

Idir Y. Epigenetic regulation of transcription from genes-containing heterochromatin : Régulation épigénétique de la transcription des gènes contenant de l’hétérochromatine. [Internet] [Doctoral dissertation]. Université Paris-Saclay (ComUE); 2019. [cited 2021 Mar 07]. Available from: http://www.theses.fr/2019SACLS270.

Council of Science Editors:

Idir Y. Epigenetic regulation of transcription from genes-containing heterochromatin : Régulation épigénétique de la transcription des gènes contenant de l’hétérochromatine. [Doctoral Dissertation]. Université Paris-Saclay (ComUE); 2019. Available from: http://www.theses.fr/2019SACLS270

University of Toronto

14. Leung, Michael Ka Kit. Inference of Computational Models of Alternative Polyadenylation and Splicing.

Degree: PhD, 2018, University of Toronto

URL: http://hdl.handle.net/1807/92091

► Instructions from the genome are first copied to make messenger RNAs, which are then translated to make proteins. To expand the repertoire of these instructions,… (more)

Subjects/Keywords: computational biology; deep learning; genomic medicine; machine learning; polyadenylation; splicing; 0715

Record Details Similar Records Cite « Share

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Leung, M. K. K. (2018). Inference of Computational Models of Alternative Polyadenylation and Splicing. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/92091

Chicago Manual of Style (16^th Edition):

Leung, Michael Ka Kit. “Inference of Computational Models of Alternative Polyadenylation and Splicing.” 2018. Doctoral Dissertation, University of Toronto. Accessed March 07, 2021. http://hdl.handle.net/1807/92091.

MLA Handbook (7^th Edition):

Leung, Michael Ka Kit. “Inference of Computational Models of Alternative Polyadenylation and Splicing.” 2018. Web. 07 Mar 2021.

Vancouver:

Leung MKK. Inference of Computational Models of Alternative Polyadenylation and Splicing. [Internet] [Doctoral dissertation]. University of Toronto; 2018. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/1807/92091.

Council of Science Editors:

Leung MKK. Inference of Computational Models of Alternative Polyadenylation and Splicing. [Doctoral Dissertation]. University of Toronto; 2018. Available from: http://hdl.handle.net/1807/92091

University of Toronto

15. Ha, Kevin C H. Systematic Analysis of Alternative Polyadenylation from High-throughput RNA Sequencing Data.

Degree: PhD, 2019, University of Toronto

URL: http://hdl.handle.net/1807/95862

► Alternative polyadenylation (APA) of pre-messenger RNA (pre-mRNA) results in the formation of multiple mature mRNA transcripts from a single gene with distinct 3′ untranslated regions… (more)

▼ Alternative polyadenylation (APA) of pre-messenger RNA (pre-mRNA) results in the formation of multiple mature mRNA transcripts from a single gene with distinct 3′ untranslated regions (3′ UTRs). It has been estimated that as many as 80% of mammalian protein-coding genes contain multiple polyadenylation (poly[A]) sites, thus contributing extensively to eukaryotic transcriptome diversity and complexity. In this thesis, I describe a new computational method, ‘Quantification of APA’ (QAPA), for profiling APA using conventional bulk RNA-seq data that accurately infers changes in APA by estimating differential 3′ UTR isoform expression. To demonstrate QAPA’s utility, I analyzed a longitudinal RNA-seq study of differentiation of mouse embryonic stem cells (ESCs) into glutamatergic neurons. By characterizing global changes of APA during this developmental process, I found a large number of genes with lengthening 3′ UTRs. These genes do not significantly overlap with those with steady-state gene expression or alternative splicing (AS) changes, indicating that APA represents a largely distinct regulatory layer. Modelling of poly(A) site usage using machine learning techniques further revealed cis-elements that are predictive of this process. I next used QAPA along with additional RNA-seq analysis tools that I helped develop to characterize the transcriptomes of different neuronal cell subtypes of the mouse hippocampus. This study revealed transcriptomic variation between different subtypes involving distinct programs of co-ordinated regulation between gene expression, AS, and APA. Among these programs, in comparing hippocampal neurons from the proximal and distal axis versus other regions, I identified a program of genes displaying differential expression of a subset of ribosomal proteins that are co-regulated with 3′ UTR lengthening of genes known to localize to the synapse. This observation suggests an important role for the coordination of local translation and mRNA localization in neurons. This also highlights the importance of profiling different post-transcriptional regulatory layers to begin to understand their contributions to cell type diversity. My thesis thus contributes new methods for profiling transcriptomes using RNA-seq data and demonstrates the utility of these methods in defining multilayered regulatory networks that underlie the development and specification of neuronal subtypes. Advisors/Committee Members: Blencowe, Benjamin J, Morris, Quaid, Molecular and Medical Genetics.

Subjects/Keywords: alternative polyadenylation; high-throughput RNA sequencing; post-transcriptional regulation; 0715

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ha, K. C. H. (2019). Systematic Analysis of Alternative Polyadenylation from High-throughput RNA Sequencing Data. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/95862

Chicago Manual of Style (16^th Edition):

Ha, Kevin C H. “Systematic Analysis of Alternative Polyadenylation from High-throughput RNA Sequencing Data.” 2019. Doctoral Dissertation, University of Toronto. Accessed March 07, 2021. http://hdl.handle.net/1807/95862.

MLA Handbook (7^th Edition):

Ha, Kevin C H. “Systematic Analysis of Alternative Polyadenylation from High-throughput RNA Sequencing Data.” 2019. Web. 07 Mar 2021.

Vancouver:

Ha KCH. Systematic Analysis of Alternative Polyadenylation from High-throughput RNA Sequencing Data. [Internet] [Doctoral dissertation]. University of Toronto; 2019. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/1807/95862.

Council of Science Editors:

Ha KCH. Systematic Analysis of Alternative Polyadenylation from High-throughput RNA Sequencing Data. [Doctoral Dissertation]. University of Toronto; 2019. Available from: http://hdl.handle.net/1807/95862

Texas Tech University

16. Hockert, John Andrew. Domains of CstF-64 and their functions in polyadenylation.

Degree: TTUHSC – Cell Biology and Biochemistry, 2007, Texas Tech University

URL: http://hdl.handle.net/2346/15998

► Polyadenylation, a critical process for expression of most eukaryotic genes, requires multiple protein factors and pre-mRNA elements. However, the essential nature of polyadenylation proteins precludes… (more)

Subjects/Keywords: Polyadenylation; Cleavage stimulation factor (CstF)

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hockert, J. A. (2007). Domains of CstF-64 and their functions in polyadenylation. (Thesis). Texas Tech University. Retrieved from http://hdl.handle.net/2346/15998

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hockert, John Andrew. “Domains of CstF-64 and their functions in polyadenylation.” 2007. Thesis, Texas Tech University. Accessed March 07, 2021. http://hdl.handle.net/2346/15998.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hockert, John Andrew. “Domains of CstF-64 and their functions in polyadenylation.” 2007. Web. 07 Mar 2021.

Vancouver:

Hockert JA. Domains of CstF-64 and their functions in polyadenylation. [Internet] [Thesis]. Texas Tech University; 2007. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/2346/15998.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hockert JA. Domains of CstF-64 and their functions in polyadenylation. [Thesis]. Texas Tech University; 2007. Available from: http://hdl.handle.net/2346/15998

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Kentucky

17. Dampanaboina, Lavanya. FUNCTIONAL CHARACTERIZATION OF WD REPEAT PROTEINS, AtCstF50 AND AtFY IN CLEAVAGE AND POLYADENYLATION.

Degree: 2011, University of Kentucky

URL: https://uknowledge.uky.edu/pss_etds/2

► Polyadenylation is an essential post-transcriptional modification resulting in a mature mRNA in eukaryotes. Three cis-elements the Far Upstream Element (FUE), Near Upstream Element (NUE), and… (more)

▼ Polyadenylation is an essential post-transcriptional modification resulting in a mature mRNA in eukaryotes. Three cis-elements the Far Upstream Element (FUE), Near Upstream Element (NUE), and Cleavage Site (CS) - guide the process of cleavage and polyadenylation with the help of multi-subunit protein complexes cleavage and polyadenylation specificity factor (CPSF), cleavage stimulation factor (CstF) along with cleavage factors and poly(A) polymerase. Protein-protein interactions play an important role in the cleavage and polyadenylation process. WD repeat proteins play an important role in protein-protein interactions and have diverse functions in plant system. In the present study WD repeat proteins AtCstF50 and AtFY were studied for their role in polyadenylation process. Mammalian CstF50 is a WD repeat protein that is one of the subunit of CstF that aids in the cleavage step by associating with CPSF and cleavage factors. AtCstF50 was functionally characterized using T-DNA knock-out lines and by identifying the proteins that interacts with it in the process. Results shows that AtCstF50 is essential and was identified as part of CPSF complex, which is different from its mammalian counter part. CPSF was known to interact with Fip (factor interacting with PAP), Poly(A) polymerase and Poly(A) binding protein and AtCstF50 also interacts with these complexes. AtFY is a 3’ end processing factor which contains WD repeats is one of the subunits of the CPSF complex in Arabidopsis polyadenylation machinery. The AtFY interacts with FCA and promotes the alternative polyadenylation and also plays a role in polyadenylation site choice of FCA mRNA. We characterized the FY expression and localization of FY in the cell by fusing with RFP reporter. Results show that FY accumulates in the nucleus while FY with deleted calmodulin binding domain localizes both to the nucleus and outside the nucleus. The individual N-terminal and C-terminal domains also localized in the nucleus suggesting that they are multiple nuclear localization signals in FY and calmodulin might play a direct or indirect role in FY localization. Using a tethering assay we proved that AtFY is able to recruit the 3’ end processing complex in the proximal polyadenylation site choice of the reporter mRNA.

Subjects/Keywords: Polyadenylation; WD repeat proteins; AtCstF50; AtFY; tethering assay; Plant Sciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dampanaboina, L. (2011). FUNCTIONAL CHARACTERIZATION OF WD REPEAT PROTEINS, AtCstF50 AND AtFY IN CLEAVAGE AND POLYADENYLATION. (Doctoral Dissertation). University of Kentucky. Retrieved from https://uknowledge.uky.edu/pss_etds/2

Chicago Manual of Style (16^th Edition):

Dampanaboina, Lavanya. “FUNCTIONAL CHARACTERIZATION OF WD REPEAT PROTEINS, AtCstF50 AND AtFY IN CLEAVAGE AND POLYADENYLATION.” 2011. Doctoral Dissertation, University of Kentucky. Accessed March 07, 2021. https://uknowledge.uky.edu/pss_etds/2.

MLA Handbook (7^th Edition):

Dampanaboina, Lavanya. “FUNCTIONAL CHARACTERIZATION OF WD REPEAT PROTEINS, AtCstF50 AND AtFY IN CLEAVAGE AND POLYADENYLATION.” 2011. Web. 07 Mar 2021.

Vancouver:

Dampanaboina L. FUNCTIONAL CHARACTERIZATION OF WD REPEAT PROTEINS, AtCstF50 AND AtFY IN CLEAVAGE AND POLYADENYLATION. [Internet] [Doctoral dissertation]. University of Kentucky; 2011. [cited 2021 Mar 07]. Available from: https://uknowledge.uky.edu/pss_etds/2.

Council of Science Editors:

Dampanaboina L. FUNCTIONAL CHARACTERIZATION OF WD REPEAT PROTEINS, AtCstF50 AND AtFY IN CLEAVAGE AND POLYADENYLATION. [Doctoral Dissertation]. University of Kentucky; 2011. Available from: https://uknowledge.uky.edu/pss_etds/2

18. Brogna, Saverio. Nonsense-mediated mRNA reduction and pre-mRNA processing in Drosophila.

Degree: PhD, 2000, Open University

URL: http://oro.open.ac.uk/54807/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323260

► From bacteria to mammalian cells, the presence of a nonsense mutation causes a reduction in the level of the mRNA of the corresponding gene. The… (more)

▼ From bacteria to mammalian cells, the presence of a nonsense mutation causes a reduction in the level of the mRNA of the corresponding gene. The reduction is not, contrary to initial expectations, due to a passive mechanism by which non translated mRNAs are degraded; rather it is a active process in which active translation, cis-acting sequences and specific trans-acting factors are required. It is generally accepted that this phenomenon is the consequence of an evolutionary conserved mechanism that evolved to protect cells from the potentially deleterious effect of truncated proteins - this is often referred to as the mRNA surveillance system or nonsense mediated mRNA decay (NMD). This phenomenon has been extensively studied in budding yeast and in mammalian systems and to a lesser extent in C. elegans. In yeast the recognition of the nonsense codon appears to occur during cytoplasmic translation and premature translation termination is thought to activate a specific protein complex - called the surveillance complex - which in tum triggers an accelerated decay of the aberrant mRNA. However, contrary to the expectation that the recognition of the nonsense codon should occur during cytoplasmic translation, several studies in mammalian cells indicate that NMD may take place in the nucleus by a mechanism that is independent of cytoplasmic translation. For example, several reports indicate that this reduction occurs while the mRNA is still associated with the nucleus, and that the stability of the cytoplasmic mRNA is unchanged relative to a wild-type allele. The common view in the field is that these apparently discordant results between NMD in yeast and in mammalian cells will eventually be accommodated in a single model in which translation in the cytoplasm plays a prominent role. For example, a commonly given explanation is that the recognition of the nonsense codon takes place during nuclear export, and it has been implied that the apparent effects on nuclear RNA are in fact triggered by the premature abortion of translation at the cytoplasmic side of the nuclear envelope. However not all the data from mammalian systems can be so easily explained by the above model. For example, several reports indicate that nonsense mutations affect the splicing of the corresponding pre-mRNA, which makes it difficult to imagine how premature translation in the cytoplasm could effect such an early event in mRNA biogenesis.

Subjects/Keywords: 572.8; RNA; Splicing; Polyadenylation; NMD

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APA (6^th Edition):

Brogna, S. (2000). Nonsense-mediated mRNA reduction and pre-mRNA processing in Drosophila. (Doctoral Dissertation). Open University. Retrieved from http://oro.open.ac.uk/54807/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323260

Chicago Manual of Style (16^th Edition):

Brogna, Saverio. “Nonsense-mediated mRNA reduction and pre-mRNA processing in Drosophila.” 2000. Doctoral Dissertation, Open University. Accessed March 07, 2021. http://oro.open.ac.uk/54807/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323260.

MLA Handbook (7^th Edition):

Brogna, Saverio. “Nonsense-mediated mRNA reduction and pre-mRNA processing in Drosophila.” 2000. Web. 07 Mar 2021.

Vancouver:

Brogna S. Nonsense-mediated mRNA reduction and pre-mRNA processing in Drosophila. [Internet] [Doctoral dissertation]. Open University; 2000. [cited 2021 Mar 07]. Available from: http://oro.open.ac.uk/54807/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323260.

Council of Science Editors:

Brogna S. Nonsense-mediated mRNA reduction and pre-mRNA processing in Drosophila. [Doctoral Dissertation]. Open University; 2000. Available from: http://oro.open.ac.uk/54807/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323260

19. Goodwin, Edward Culver. The dissection of the bovine growth hormone polyadenylation signal reveals a complex element within the 3' flanking sequence.

Degree: PhD, Molecular Biology and Microbiology, 1993, Case Western Reserve University School of Graduate Studies

URL: http://rave.ohiolink.edu/etdc/view?acc_num=case1057174645

► In addition to the conserved AAUAAA hexanucleotide, GU and U-rich sequences in the 3′ flanking region are thought to be critical for the efficient polyadenylation… (more)

Subjects/Keywords: Biology, Molecular; polyadenylation flanking sequence

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APA (6^th Edition):

Goodwin, E. C. (1993). The dissection of the bovine growth hormone polyadenylation signal reveals a complex element within the 3' flanking sequence. (Doctoral Dissertation). Case Western Reserve University School of Graduate Studies. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=case1057174645

Chicago Manual of Style (16^th Edition):

Goodwin, Edward Culver. “The dissection of the bovine growth hormone polyadenylation signal reveals a complex element within the 3' flanking sequence.” 1993. Doctoral Dissertation, Case Western Reserve University School of Graduate Studies. Accessed March 07, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1057174645.

MLA Handbook (7^th Edition):

Goodwin, Edward Culver. “The dissection of the bovine growth hormone polyadenylation signal reveals a complex element within the 3' flanking sequence.” 1993. Web. 07 Mar 2021.

Vancouver:

Goodwin EC. The dissection of the bovine growth hormone polyadenylation signal reveals a complex element within the 3' flanking sequence. [Internet] [Doctoral dissertation]. Case Western Reserve University School of Graduate Studies; 1993. [cited 2021 Mar 07]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1057174645.

Council of Science Editors:

Goodwin EC. The dissection of the bovine growth hormone polyadenylation signal reveals a complex element within the 3' flanking sequence. [Doctoral Dissertation]. Case Western Reserve University School of Graduate Studies; 1993. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1057174645

Miami University

20. Chen, Jie. Alternative polyadenylation regulates the expression of the light harvesting gene LHCB4.1 in Arabidopsis mutant oxt6.

Degree: MS, Botany, 2011, Miami University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=miami1322534400

► Recent studies revealed differential usage of Alternative Polyadenylation (APA) in Arabidopsis thaliana wild-type and the oxt6 mutant in which the Oxidative Stress Tolerance 6 gene… (more)

Subjects/Keywords: Botany; oxt6; alternative polyadenylation; LHCB4.1

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APA (6^th Edition):

Chen, J. (2011). Alternative polyadenylation regulates the expression of the light harvesting gene LHCB4.1 in Arabidopsis mutant oxt6. (Masters Thesis). Miami University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=miami1322534400

Chicago Manual of Style (16^th Edition):

Chen, Jie. “Alternative polyadenylation regulates the expression of the light harvesting gene LHCB4.1 in Arabidopsis mutant oxt6.” 2011. Masters Thesis, Miami University. Accessed March 07, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=miami1322534400.

MLA Handbook (7^th Edition):

Chen, Jie. “Alternative polyadenylation regulates the expression of the light harvesting gene LHCB4.1 in Arabidopsis mutant oxt6.” 2011. Web. 07 Mar 2021.

Vancouver:

Chen J. Alternative polyadenylation regulates the expression of the light harvesting gene LHCB4.1 in Arabidopsis mutant oxt6. [Internet] [Masters thesis]. Miami University; 2011. [cited 2021 Mar 07]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=miami1322534400.

Council of Science Editors:

Chen J. Alternative polyadenylation regulates the expression of the light harvesting gene LHCB4.1 in Arabidopsis mutant oxt6. [Masters Thesis]. Miami University; 2011. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=miami1322534400

Miami University

21. Yingdong, Zhu. Analysis of Novel 5'-UTR Polyadenylation Sites in Arabidopsis thaliana.

Degree: MS, Cell, Molecular and Structural Biology (CMSB), 2016, Miami University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=miami1480717686996059

► Messenger RNA (mRNA) polyadenylation is an indispensable step during post-transcriptional pre-mRNA processing in eukaryotes. The usage of one poly(A) site over another is known as… (more)

Subjects/Keywords: Biology; 5-UTR; alternative polyadenylation; open reading frame

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APA (6^th Edition):

Yingdong, Z. (2016). Analysis of Novel 5'-UTR Polyadenylation Sites in Arabidopsis thaliana. (Masters Thesis). Miami University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=miami1480717686996059

Chicago Manual of Style (16^th Edition):

Yingdong, Zhu. “Analysis of Novel 5'-UTR Polyadenylation Sites in Arabidopsis thaliana.” 2016. Masters Thesis, Miami University. Accessed March 07, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=miami1480717686996059.

MLA Handbook (7^th Edition):

Yingdong, Zhu. “Analysis of Novel 5'-UTR Polyadenylation Sites in Arabidopsis thaliana.” 2016. Web. 07 Mar 2021.

Vancouver:

Yingdong Z. Analysis of Novel 5'-UTR Polyadenylation Sites in Arabidopsis thaliana. [Internet] [Masters thesis]. Miami University; 2016. [cited 2021 Mar 07]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=miami1480717686996059.

Council of Science Editors:

Yingdong Z. Analysis of Novel 5'-UTR Polyadenylation Sites in Arabidopsis thaliana. [Masters Thesis]. Miami University; 2016. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=miami1480717686996059

Colorado State University

22. Sagawa, Fumihiko. Nucleophosmin deposition during mRNA 3' end processing influences poly(A) tail length and mRNA export.

Degree: MS(M.S.), Cell and Molecular Biology, 2011, Colorado State University

URL: http://hdl.handle.net/10217/47448

► During polyadenylation the multi-functional protein nucleophosmin is deposited onto all cellular mRNAs analyzed. Premature termination of poly(A) tail synthesis using cordycepin abrogates deposition of the… (more)

Subjects/Keywords: mRNA export; Nucleophosmin; polyadenylation; poly(A) tail; RNA

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APA (6^th Edition):

Sagawa, F. (2011). Nucleophosmin deposition during mRNA 3' end processing influences poly(A) tail length and mRNA export. (Masters Thesis). Colorado State University. Retrieved from http://hdl.handle.net/10217/47448

Chicago Manual of Style (16^th Edition):

Sagawa, Fumihiko. “Nucleophosmin deposition during mRNA 3' end processing influences poly(A) tail length and mRNA export.” 2011. Masters Thesis, Colorado State University. Accessed March 07, 2021. http://hdl.handle.net/10217/47448.

MLA Handbook (7^th Edition):

Sagawa, Fumihiko. “Nucleophosmin deposition during mRNA 3' end processing influences poly(A) tail length and mRNA export.” 2011. Web. 07 Mar 2021.

Vancouver:

Sagawa F. Nucleophosmin deposition during mRNA 3' end processing influences poly(A) tail length and mRNA export. [Internet] [Masters thesis]. Colorado State University; 2011. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/10217/47448.

Council of Science Editors:

Sagawa F. Nucleophosmin deposition during mRNA 3' end processing influences poly(A) tail length and mRNA export. [Masters Thesis]. Colorado State University; 2011. Available from: http://hdl.handle.net/10217/47448

University of Rochester

23. Schmidt, Karyn A. Air Proteins Control Differential TRAMP Substrate Specificity for Nuclear RNA Surveillance.

Degree: PhD, 2013, University of Rochester

URL: http://hdl.handle.net/1802/26784

► The Saccharomyces cerevisiae TRAMP4 and TRAMP5 complexes, which consist of the poly(A) polymerase Trf4 or Trf5, respectively, the zinc knuckle proteins Air1 or Air2, and… (more)

Subjects/Keywords: Air1; Air2; Noncoding RNAs; RNA Exosome; TRAMP Complex; Rrp6; Dis3; Rrp44; 2Micron Plasmid; Polyadenylation

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APA (6^th Edition):

Schmidt, K. A. (2013). Air Proteins Control Differential TRAMP Substrate Specificity for Nuclear RNA Surveillance. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/26784

Chicago Manual of Style (16^th Edition):

Schmidt, Karyn A. “Air Proteins Control Differential TRAMP Substrate Specificity for Nuclear RNA Surveillance.” 2013. Doctoral Dissertation, University of Rochester. Accessed March 07, 2021. http://hdl.handle.net/1802/26784.

MLA Handbook (7^th Edition):

Schmidt, Karyn A. “Air Proteins Control Differential TRAMP Substrate Specificity for Nuclear RNA Surveillance.” 2013. Web. 07 Mar 2021.

Vancouver:

Schmidt KA. Air Proteins Control Differential TRAMP Substrate Specificity for Nuclear RNA Surveillance. [Internet] [Doctoral dissertation]. University of Rochester; 2013. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/1802/26784.

Council of Science Editors:

Schmidt KA. Air Proteins Control Differential TRAMP Substrate Specificity for Nuclear RNA Surveillance. [Doctoral Dissertation]. University of Rochester; 2013. Available from: http://hdl.handle.net/1802/26784

Harvard University

24. Dickson, John Robert. The Role of the Human Tau 3'-Untranslated Region in Regulating Tau Expression.

Degree: PhD, Biology: Medical Sciences, Division of, 2013, Harvard University

URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11181167

► The microtubule-associated protein tau forms pathological neuronal filaments in Alzheimer's disease (AD) and other neurodegenerative disorders, known collectively as tauopathies. Previous studies in transgenic mouse… (more)

▼ The microtubule-associated protein tau forms pathological neuronal filaments in Alzheimer's disease (AD) and other neurodegenerative disorders, known collectively as tauopathies. Previous studies in transgenic mouse models of AD suggest that reducing tau expression may be safe and beneficial for the prevention or treatment of AD and possibly other tauopathies. As a first step toward identifying novel therapeutic strategies to reduce tau levels, the studies presented in this dissertation aim to investigate the role of the human tau 3'-untranslated region (3'-UTR) in regulating tau expression. Tau expresses two 3'-UTR isoforms, long and short, as a result of alternative polyadenylation. The exact sequence of these two 3'-UTR isoforms was determined by rapid amplification of cDNA 3'-ends (3'-RACE), and the two 3'-UTR isoforms were cloned into a luciferase reporter vector. Using these reporter constructs, the expression of these isoforms was found to be differentially controlled in human neuroblastoma cell lines M17D and SH-SY5Y by luciferase assays and quantitative PCR (qPCR). Through an unbiased screen of tau 3'-UTR deletions and fragments using luciferase reporter constructs, several regions in the long tau 3'-UTR isoform that contain regulatory cis-elements were identified. Additionally, several microRNAs were computationally identified as candidates that might bind the long tau 3'-UTR and thereby differentially control the expression of long versus short tau 3'-UTR isoforms. Screening these candidate microRNAs via luciferase reporter assay identified miR-34a, which was subsequently shown to repress the expression of endogenous tau protein and mRNA in M17D cells using Western blot and qPCR, respectively. Conversely, inhibition of endogenously expressed miR-34 family members leads to increased endogenous tau expression. Taken together, these studies suggest that the expression of the two tau 3'-UTR isoforms is differentially regulated and that this differential regulation is due to the presence of regulatory cis-elements found only in the long tau 3'-UTR isoform, including a binding site for miR-34 family members. Improved understanding of the regulation of tau expression by its 3'-UTR may ultimately lead to the development of novel therapeutic strategies for the treatment of Alzheimer's disease and other tauopathies. Advisors/Committee Members: Wolfe, Michael S. (advisor), Buratowski, Stephen (committee member), Gregory, Richard (committee member), Krichevsky, Anna (committee member), Tsai, Li-Huei (committee member).

Subjects/Keywords: Molecular biology; Neurosciences; 3'-untranslated region; Alternative polyadenylation; Alzheimer's disease; MAPT; miR-34a; Tau

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APA (6^th Edition):

Dickson, J. R. (2013). The Role of the Human Tau 3'-Untranslated Region in Regulating Tau Expression. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:11181167

Chicago Manual of Style (16^th Edition):

Dickson, John Robert. “The Role of the Human Tau 3'-Untranslated Region in Regulating Tau Expression.” 2013. Doctoral Dissertation, Harvard University. Accessed March 07, 2021. http://nrs.harvard.edu/urn-3:HUL.InstRepos:11181167.

MLA Handbook (7^th Edition):

Dickson, John Robert. “The Role of the Human Tau 3'-Untranslated Region in Regulating Tau Expression.” 2013. Web. 07 Mar 2021.

Vancouver:

Dickson JR. The Role of the Human Tau 3'-Untranslated Region in Regulating Tau Expression. [Internet] [Doctoral dissertation]. Harvard University; 2013. [cited 2021 Mar 07]. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11181167.

Council of Science Editors:

Dickson JR. The Role of the Human Tau 3'-Untranslated Region in Regulating Tau Expression. [Doctoral Dissertation]. Harvard University; 2013. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11181167

Texas Medical Center

25. Peart, Natoya J. INTERROGATING DUX4 MRNA 3′ END PROCESSING.

Degree: PhD, 2016, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/692

► Double Homeobox 4, Dux4, is the leading candidate gene for Facioscapulohumeral Dystrophy (FSHD). FSHD is the third most common muscular dystrophy, and is characterized… (more)

▼ Double Homeobox 4, Dux4, is the leading candidate gene for Facioscapulohumeral Dystrophy (FSHD). FSHD is the third most common muscular dystrophy, and is characterized by progressive muscle weakness primarily in the upper body. In individuals diagnosed with FSHD, Dux4 is inappropriately expressed in somatic cells due to two conditions. The first is hypomethylation of the subtelomeric D4Z4 repeats on chromosome 4. Each D4Z4 repeat on chromosome 4 is 3.3kb in length and contains the open reading frame for Dux4. Hypomethylation of the D4Z4 repeats primarily occurs due to contraction of the repeats from 11-100 (typical numbers in the healthy population) to between 1 and 10 repeats. Concomitant with the hypomethylation of the D4Z4 repeats on chromosome 4 is a single nucleotide polymorphism in the flanking DNA that generates a non-consensus polyadenylation signal (PAS). This PAS allows for the productive transcription of a polyadenylated Dux4 mRNA from the terminal D4Z4 repeat. Dux4 is anemically expressed in patient somatic cells, but contributes to FSHD pathology due to Dux4-dependent cellular reprogramming. We aim to understand what regulatory elements facilitate the cleavage and polyadenylation (CPA) of the Dux4 mRNA beyond the non-consensus PAS and to determine if inefficient CPA underlies the poor expression of Dux4 in patient cells. We designed a transcriptional read-through reporter to assay cleavage and polyadenylation in cells and confirm that additional cis elements are required for CPA of Dux4 besides the non-consensus PAS. This element is located outside the region where cis regulatory elements for CPA are usually present. Moreover, the element which lies downstream of the PAS, is within a degenerate repeat region, called β-satellite DNA. Using the knowledge gained from characterizing Dux4 mRNA 3′end formation, we designed antisense oligonucleotides (ASOs) to impair the production of polyadenylated Dux4. Prior to antagonizing Dux4 CPA, we demonstrate, in proof of principle experiments that ASOs directed toward required CPA regulatory elements can impair gene expression, and may redirect polyadenylation. Finally, the work presented here lays the foundation for us to impair Dux4 CPA in reporter driven assays and patient cells; and to exploit currently available deep sequencing technology to determine the specificity of PAS-directed ASOs. Advisors/Committee Members: Eric J Wagner, PhD., Joseph Alcorn, PhD., Swathi Arur, PhD..

Subjects/Keywords: cleavage and polyadenylation; Facioscapulohumeral Dystrophy; antisense oligonucleotides; Life Sciences; Medicine and Health Sciences

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APA (6^th Edition):

Peart, N. J. (2016). INTERROGATING DUX4 MRNA 3′ END PROCESSING. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/692

Chicago Manual of Style (16^th Edition):

Peart, Natoya J. “INTERROGATING DUX4 MRNA 3′ END PROCESSING.” 2016. Doctoral Dissertation, Texas Medical Center. Accessed March 07, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/692.

MLA Handbook (7^th Edition):

Peart, Natoya J. “INTERROGATING DUX4 MRNA 3′ END PROCESSING.” 2016. Web. 07 Mar 2021.

Vancouver:

Peart NJ. INTERROGATING DUX4 MRNA 3′ END PROCESSING. [Internet] [Doctoral dissertation]. Texas Medical Center; 2016. [cited 2021 Mar 07]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/692.

Council of Science Editors:

Peart NJ. INTERROGATING DUX4 MRNA 3′ END PROCESSING. [Doctoral Dissertation]. Texas Medical Center; 2016. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/692

University of Adelaide

26. McCarthy, Peter James. Investigation into the molecular function of the neuronal Hu RNA binding protein, HuCsv1.

Degree: 2011, University of Adelaide

URL: http://hdl.handle.net/2440/70239

► Of the four Hu genes found in most vertebrates (HuA, HuB, HuC and HuD), all except HuA exhibit mRNA and protein expression that is essentially… (more)

▼ Of the four Hu genes found in most vertebrates (HuA, HuB, HuC and HuD), all except HuA exhibit mRNA and protein expression that is essentially restricted to post-mitotic neurons of the developing and adult nervous systems. Spatial and temporal examination of individual “neuronal Hu” (nHu = HuB, HuC and HuD) proteins in brain tissue suggests nHu proteins may play a functional role during neuronal differentiation; as RNA-binding proteins, the nHu proteins may participate in gene regulatory events that are essential for acquisition of the neuronal phenotype. We have identified a number of candidate mRNA targets of the nHu proteins. Our data suggest that the majority of these mRNAs interact with nHu proteins through sequences present in their 3´ untranslated regions (UTRs). From this 3´UTR target subset, several mRNAs were selected for further examination based on reported roles for their encoded proteins during axonogenesis, a critical developmental process during which nascent neurons grow and extend axons that eventually connect to and form synaptic connections with other neurons. The mRNAs chosen encode for cytoskeleton-modifying proteins; Cofilin, Vasodilator-Stimulated Phosphoprotein (VASP) and the Rho GTPase Cdc42. The primary aim of the work reported in this thesis was to characterise the effect of interactions between the neuronal Hu protein HuC, and the CLIP-identified 3´UTRs listed above. To do this, the 3´UTR sequences were cloned into reporter vectors (both fluorescent and luciferase reporter-based) to produce reporter protein-encoding messages that included a putative target 3´UTR. These vectors were then used in co-transfection experiments with or without HuC and measurements of reporter protein and mRNA abundance obtained. Interestingly, despite initial speculation that HuC might be involved in directly regulating protein expression from target mRNAs, no significant effect of HuC on protein production from any of the 3´UTR-reporter mRNAs tested was observed. However and quite unexpectedly, measurement of 3´UTR-reporter mRNA abundance from co-transfection assays revealed a potential role for HuC in modulating alternative polyadenylation site choice for one of the CLIP-identified 3´UTR sequences. Regulation of mRNA polyadenylation site choice may be a novel mechanism by which nHu proteins post-transcriptionally control gene expression during neuronal development. Advisors/Committee Members: Jensen, Kirk Blomquist (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: post-transcriptional gene regulation; RNA binding proteins; polyadenylation; aternative splicing; neuronal development

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APA (6^th Edition):

McCarthy, P. J. (2011). Investigation into the molecular function of the neuronal Hu RNA binding protein, HuCsv1. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/70239

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

McCarthy, Peter James. “Investigation into the molecular function of the neuronal Hu RNA binding protein, HuCsv1.” 2011. Thesis, University of Adelaide. Accessed March 07, 2021. http://hdl.handle.net/2440/70239.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

McCarthy, Peter James. “Investigation into the molecular function of the neuronal Hu RNA binding protein, HuCsv1.” 2011. Web. 07 Mar 2021.

Vancouver:

McCarthy PJ. Investigation into the molecular function of the neuronal Hu RNA binding protein, HuCsv1. [Internet] [Thesis]. University of Adelaide; 2011. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/2440/70239.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

McCarthy PJ. Investigation into the molecular function of the neuronal Hu RNA binding protein, HuCsv1. [Thesis]. University of Adelaide; 2011. Available from: http://hdl.handle.net/2440/70239

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

New Jersey Institute of Technology

27. Ling, Xiao. Polyaseeker: a computational framework for identifying polyadenylation cleavage site from RNA-seq.

Degree: MSin Bioinformatics - (M.S.), Computer Science, 2013, New Jersey Institute of Technology

URL: https://digitalcommons.njit.edu/theses/169

► Alternative polyadenylation (APA) of mRNA plays a crucial role for post-transcriptional gene regulation. Recently, advances in next generation sequencing technology have made it possible… (more)

Subjects/Keywords: Post-transcriptional gene regulation; Alternative polyadenylation (APA) of mRNA; Bioinformatics; Computer Sciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ling, X. (2013). Polyaseeker: a computational framework for identifying polyadenylation cleavage site from RNA-seq. (Thesis). New Jersey Institute of Technology. Retrieved from https://digitalcommons.njit.edu/theses/169

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ling, Xiao. “Polyaseeker: a computational framework for identifying polyadenylation cleavage site from RNA-seq.” 2013. Thesis, New Jersey Institute of Technology. Accessed March 07, 2021. https://digitalcommons.njit.edu/theses/169.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ling, Xiao. “Polyaseeker: a computational framework for identifying polyadenylation cleavage site from RNA-seq.” 2013. Web. 07 Mar 2021.

Vancouver:

Ling X. Polyaseeker: a computational framework for identifying polyadenylation cleavage site from RNA-seq. [Internet] [Thesis]. New Jersey Institute of Technology; 2013. [cited 2021 Mar 07]. Available from: https://digitalcommons.njit.edu/theses/169.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ling X. Polyaseeker: a computational framework for identifying polyadenylation cleavage site from RNA-seq. [Thesis]. New Jersey Institute of Technology; 2013. Available from: https://digitalcommons.njit.edu/theses/169

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Freie Universität Berlin

28. Xiao, Meisheng. Analyse des cis-regulatorischen Effekts auf alternative Polyadenylierung mittels Hybrid-Mäusen.

Degree: 2016, Freie Universität Berlin

URL: http://dx.doi.org/10.17169/refubium-11504

► Die 3’-Enden der meisten eukaryotischen mRNAs werden im letzten Schritt der Transkription geschnitten und polyadenyliert. Jüngere Studien haben gezeigt, dass mehr als 70% der Gene… (more)

▼ Die 3’-Enden der meisten eukaryotischen mRNAs werden im letzten Schritt der Transkription geschnitten und polyadenyliert. Jüngere Studien haben gezeigt, dass mehr als 70% der Gene von Säugetieren mehrere Polyadenylierungsstellen (pAs) haben. Diese ermöglichen die Generierung mehrer mRNA-Isoformen mit unterschiedlichen kodierenden oder 3‘-untranslatierten Regionen (3’UTR) aus demselben Genlokus und tragen zur Komplexität des Transkriptoms und des Proteoms bei durch Regulation ihrer Stabilität, Lokalisierung, Translation und Funktion. Mittels Einsatz von „large scale“-Technologien konnte die umfassende und dynamische Regulation des 3’UTRs durch alternative Polyadenylierung (APA) in verschiednenen Geweben gezeigt werden, sowie in verschiedenen zellulären Kontexten (Proliferation, Differenzierung und Entwicklung) und als Antwort auf Stimulation. Obwohl der genaue APA-Mechanismus noch untersucht wird, sollte er generell durch die Interaktion von cis-regulatorischen Elementen innerhalb der DNA oder RNA mit trans-Faktoren inklusive des polyadenylation cleavage core protein complex sowie zusätzlicher RNA-bindender Proteine (RBPs) vermittelt werden. Die Veränderungen von globalen APA-Mustern während der Evolution sind wenig untersucht. Solche Veränderungen können aus der Divergenz von cis- regulatorischen Elementen und/oder trans-agierenden RBPs entstehen. Die Divergenzen der zwei Faktoren mit unterschiedlichem Ausmass an pleiotropen Konsequenzen verlaufen in unterschiedlichen evolutionären Bahnen. Deswegen ist es wichtig, die relativen Beiträge von cis- und trans-Effekten zu unterscheiden, um die Evolution von APA besser zu verstehen. Um den Beitrag von cis-und trans-agierenden Faktoren im APA-Prozess in einem Säugetiersystem umfassend zu untersuchen, haben wir in diesem Projekt pAs usage zwischen zwei parentalen Mausstämmen (C57BL/6J and SPRET/EiJ) und zwischen zwei Allelen von Hybriden der F1-Generation mittels 3’ read capturing and sequencing (3’ READS) and 3’ mRNA sequencing identifiziert und quantifiziert. Insgesamt haben wir 3850 parentale, divergente pAs innerhalb von 5 APA-Typen zwischen den beiden parentalen Mausstämmen identifiziert. Durch den Vergleich der parental- divergenten pAs mit denen der Hybride der F1-Generation konnten wir beobachten, dass vorrangig cis-regulatorische Elemente einen Effekt auf die pAs usage haben, welcher durch genetische Varianten um die pAs herum herbeigeführt wird. Weitere Analysen der Sequenzeigenschaften konnten demonstrieren, dass instabile Sekundärstruktur sowie ein neuartiges UUUUUU- hexamer in der der pAs vorangehenden Region die pAs usage verstärken bzw. inhibieren können. Advisors/Committee Members: [email protected] (contact), [email protected] (contact), m (gender), Prof. Dr. Wei Chen (firstReferee), Prof. Dr. Markus Wahl (furtherReferee).

Subjects/Keywords: alternative polyadenylation; evolution; divergence; 500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::572 Biochemie

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APA (6^th Edition):

Xiao, M. (2016). Analyse des cis-regulatorischen Effekts auf alternative Polyadenylierung mittels Hybrid-Mäusen. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-11504

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Xiao, Meisheng. “Analyse des cis-regulatorischen Effekts auf alternative Polyadenylierung mittels Hybrid-Mäusen.” 2016. Thesis, Freie Universität Berlin. Accessed March 07, 2021. http://dx.doi.org/10.17169/refubium-11504.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Xiao, Meisheng. “Analyse des cis-regulatorischen Effekts auf alternative Polyadenylierung mittels Hybrid-Mäusen.” 2016. Web. 07 Mar 2021.

Vancouver:

Xiao M. Analyse des cis-regulatorischen Effekts auf alternative Polyadenylierung mittels Hybrid-Mäusen. [Internet] [Thesis]. Freie Universität Berlin; 2016. [cited 2021 Mar 07]. Available from: http://dx.doi.org/10.17169/refubium-11504.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Xiao M. Analyse des cis-regulatorischen Effekts auf alternative Polyadenylierung mittels Hybrid-Mäusen. [Thesis]. Freie Universität Berlin; 2016. Available from: http://dx.doi.org/10.17169/refubium-11504

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Lund

29. Nilsson, Kersti. The role of cellular RNA processing functions in Human papillomavirus type 16 gene regulation.

Degree: 2019, University of Lund

URL: https://lup.lub.lu.se/record/caa4cff4-3dc2-4659-bd09-8e97ce6e6511 ; https://portal.research.lu.se/ws/files/70160736/kappa.pdf

► AbstractInfections with Human papillomavirus type 16 (HPV16) is the most the most common, sexually transferred and is responsible for genital warts, cervical cancers and a… (more)

▼ AbstractInfections with Human papillomavirus type 16 (HPV16) is the most the most common, sexually transferred and is responsible for genital warts, cervical cancers and a growing number of head and neck cancers. Knowledge about how HPV16 interacts with the infected cell to regulate its gene expression is essential for therapeutic development. Here, we show that the viral E5 protein which may contribute to carcinogenesis can only be expressed efficiently during the early infection. E5 is the last open reading frame (ORF) on the early pre-mRNAs. Therefore, its expression requires removal of upstream, inhibitory E7 and E1 ORFs by alternative splicing. Alternative splicing is also required for HPV16 later gene expression together with an inhibition of the early polyadenylation signal. We report that induction of the DNA damage response (DDR) by alkylating agent melphalan caused both an activation of late gene splicing and inhibition of the early polyadenylation signal. The connection between induction of DDR and HPV16 late gene expression by melphalan was dependent on ATM signaling and caused an accumulation of phosphorylated BRCA1 on HPV16 DNA. BRAC1 also interacted with splice factors U2AF65 and hnRNPC that were recruited to HPV16 mRNAs to generate a expression of late, L1 and L2 HPV16 mRNAs. The ATM-branch of the DDR is hijacked by HPV for productive viral replication prior to late gene expression. Therefore, we suggest that HPV16 also has evolved to utilize the connection between DDR and RNA-processing for late gene activation. Finally, we investigated the presence of methylated N6-adenosine (m6A) on HPV16 mRNAs in connection to regulation of alternative splicing. Here, we report that HPV16 mRNAs undergoes methylation and that the proteins associated with m6A affects viral splicing. In particular, splicing of mRNAs that express the viral oncoproteins E6 and E7 were affected in a mutually exclusive manner. The same pattern was also observed for mRNAs expressing viral replication proteins E1 and E2. Further investigations will reveal the true regulatory importance of m6A for splicing of these mRNAs. In conclusion, this thesis identifies the main E5 mRNA, connects HPV16 late gene expression to the DDR and suggests a regulatory function of m6A in HPV16 alternative splicing.

Subjects/Keywords: Medical and Health Sciences; RNA Splicing; Polyadenylation; DNA damage response, Human papillomavirus; Influenza A

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Nilsson, K. (2019). The role of cellular RNA processing functions in Human papillomavirus type 16 gene regulation. (Doctoral Dissertation). University of Lund. Retrieved from https://lup.lub.lu.se/record/caa4cff4-3dc2-4659-bd09-8e97ce6e6511 ; https://portal.research.lu.se/ws/files/70160736/kappa.pdf

Chicago Manual of Style (16^th Edition):

Nilsson, Kersti. “The role of cellular RNA processing functions in Human papillomavirus type 16 gene regulation.” 2019. Doctoral Dissertation, University of Lund. Accessed March 07, 2021. https://lup.lub.lu.se/record/caa4cff4-3dc2-4659-bd09-8e97ce6e6511 ; https://portal.research.lu.se/ws/files/70160736/kappa.pdf.

MLA Handbook (7^th Edition):

Nilsson, Kersti. “The role of cellular RNA processing functions in Human papillomavirus type 16 gene regulation.” 2019. Web. 07 Mar 2021.

Vancouver:

Nilsson K. The role of cellular RNA processing functions in Human papillomavirus type 16 gene regulation. [Internet] [Doctoral dissertation]. University of Lund; 2019. [cited 2021 Mar 07]. Available from: https://lup.lub.lu.se/record/caa4cff4-3dc2-4659-bd09-8e97ce6e6511 ; https://portal.research.lu.se/ws/files/70160736/kappa.pdf.

Council of Science Editors:

Nilsson K. The role of cellular RNA processing functions in Human papillomavirus type 16 gene regulation. [Doctoral Dissertation]. University of Lund; 2019. Available from: https://lup.lub.lu.se/record/caa4cff4-3dc2-4659-bd09-8e97ce6e6511 ; https://portal.research.lu.se/ws/files/70160736/kappa.pdf

University of Minnesota

30. Zhang, Wei. Computational Analysis of Transcript Interactions and Variants in Cancer.

Degree: PhD, Computer Science, 2015, University of Minnesota

URL: http://hdl.handle.net/11299/177090

► New sequencing and array technologies for transcriptome-wide profiling of RNAs have greatly promoted the interest in gene and isoform-based functional characterizations of a cellular system.… (more)

▼ New sequencing and array technologies for transcriptome-wide profiling of RNAs have greatly promoted the interest in gene and isoform-based functional characterizations of a cellular system. Many statistical and machine learning methods have been developed to quantify the isoform/gene expression and identify the transcript variants for cancer outcome prediction. Since building reliable learning models for cancer transcriptome analysis relies on accurate modeling of prior knowledge and interactions between the cellular components, it is still a computational challenge. This thesis proposes several robust and reliable learning models to integrate both large-scale array and sequencing data with biological prior knowledge for cancer transcriptome analysis. First, we explore two signed network propagation algorithms and general optimization frameworks for detecting differential gene expressions and DNA copy number variations (CNV). Second, we present a network-based Cox regression model called Net-Cox and applied Net-Cox for a large-scale survival analysis across multiple ovarian cancer datasets to identify highly consistent signature genes and improve the accuracy of survival prediction. Third, we introduce a Network-based method for RNA-Seq-based Transcript Quantification (Net-RSTQ) to integrate protein domain-domain interaction network with short read alignments for transcript abundance estimation. Finally, we perform computational analysis of mRNA 3'-UTR shortening on mouse embryonic fibroblast (MEF) cell lines to understand changes of molecular features on dysregulated activation of mammalian target of rapamycin (mTOR). We evaluate our models and findings with simulations and real genomic datasets. The results suggest that our models explore the global topological information in the networks, improve the transcript quantification for better sample classification, identified consistent biomarkers to improve cancer prognosis and survival prediction. The analysis of 3'-UTR with RNA-Seq data find an unexpected link between mTOR and ubiquitin-mediated proteolysis pathway through 3'-UTR shortening.

Subjects/Keywords: Alternative Polyadenylation; Alternative Splicing; Cancer Transcriptome; Machine Learning; Network-based models; RNA-Seq

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zhang, W. (2015). Computational Analysis of Transcript Interactions and Variants in Cancer. (Doctoral Dissertation). University of Minnesota. Retrieved from http://hdl.handle.net/11299/177090

Chicago Manual of Style (16^th Edition):

Zhang, Wei. “Computational Analysis of Transcript Interactions and Variants in Cancer.” 2015. Doctoral Dissertation, University of Minnesota. Accessed March 07, 2021. http://hdl.handle.net/11299/177090.

MLA Handbook (7^th Edition):

Zhang, Wei. “Computational Analysis of Transcript Interactions and Variants in Cancer.” 2015. Web. 07 Mar 2021.

Vancouver:

Zhang W. Computational Analysis of Transcript Interactions and Variants in Cancer. [Internet] [Doctoral dissertation]. University of Minnesota; 2015. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/11299/177090.

Council of Science Editors:

Zhang W. Computational Analysis of Transcript Interactions and Variants in Cancer. [Doctoral Dissertation]. University of Minnesota; 2015. Available from: http://hdl.handle.net/11299/177090

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Open Access Theses and Dissertations