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University of Illinois – Urbana-Champaign
1.
Sadeque, Ahmed.
Identification of alternative exon usage in cancer survival using hierarchical modeling.
Degree: MS, 4026, 2012, University of Illinois – Urbana-Champaign
URL: http://hdl.handle.net/2142/34549 
► Background Alternative exon usage (AEU) is an important component of gene expression regulation. Exon expression platforms allow the detection of associations between AEU and phenotypes…
(more)
▼ Background
Alternative exon usage (AEU) is an important component of gene expression regulation. Exon expression platforms allow the detection of associations between AEU and phenotypes such
as cancer. Numerous studies have identified associations between gene expression and the brain cancer glioblastoma multiforme (GBM). The few consistent gene expression biomarkers of GBM that have been reported may be due to the limited consideration of AEU and the analytical approaches used. The objectives of this study were to develop a model that accounts for the
variations in expression present between the exons within a gene and to identify AEU biomarkers of GBM survival.
Methods
The expression of exons corresponding to 25,403 genes was related to the survival of 250
individuals diagnosed with GBM in a training data set. Genes exhibiting AEU in the training
data set were confirmed in an independent validation data set of 78 patients. A hierarchical
model allows the consideration of covariation between exons within a gene and of the effect of
the epidemiological characteristics of the patients was developed to identify associations
between exon expression and patient survival. The same model serves multi-exon models with
and without AEU and single-exon models.
Results
AEU associated with GBM survival was identified on 2477 genes (P-value < 5.0E-04 (FDR adjusted P-value < 5.0E-04). G-protein coupled receptor 98 (Gpr98) and epidermal growth factor (Egf) were among the genes exhibiting AEU with 30 and 9 exons associated with GBM survival, respectively. Pathways enriched among the AEU genes included focal adhesion, ECM-receptor interaction, ABC transporters and pathways in cancer. In addition, 24 multi-exon genes without AEU and 8 single-exon genes were associated with GBM survival (P-value < 0.0005).
Conclusions
The inferred patterns of AEU were consistent with in silico
AS models. The hierarchical model used offered a flexible and simple way to interpret and identify associations between survival that accommodates multi-exon genes with or without AEU and single exon genes.
Advisors/Committee Members: Rodriguez-Zas, Sandra L. (advisor).
Subjects/Keywords: Alternative Splicing (AS); Alternative Exon Usage (AEU); Glioblastoma (GBM)
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APA (6th Edition):
Sadeque, A. (2012). Identification of alternative exon usage in cancer survival using hierarchical modeling. (Thesis). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/34549
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Sadeque, Ahmed. “Identification of alternative exon usage in cancer survival using hierarchical modeling.” 2012. Thesis, University of Illinois – Urbana-Champaign. Accessed February 27, 2021.
http://hdl.handle.net/2142/34549.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Sadeque, Ahmed. “Identification of alternative exon usage in cancer survival using hierarchical modeling.” 2012. Web. 27 Feb 2021.
Vancouver:
Sadeque A. Identification of alternative exon usage in cancer survival using hierarchical modeling. [Internet] [Thesis]. University of Illinois – Urbana-Champaign; 2012. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/2142/34549.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Sadeque A. Identification of alternative exon usage in cancer survival using hierarchical modeling. [Thesis]. University of Illinois – Urbana-Champaign; 2012. Available from: http://hdl.handle.net/2142/34549
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
2.
Phillips, Cecilia G.
Alternative Splicing Controls G Protein Inhibition of CaV2.2
Calcium Channels.
Degree: PhD, Neuroscience, 2012, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:297699/
► CaV2.2 voltage-gated calcium channels (CaVs) are expressed at presynaptic terminals in most central and peripheral neurons where they control the calcium (Ca2+) entry that triggers…
(more)
▼ CaV2.2 voltage-gated calcium channels (CaVs) are
expressed at presynaptic terminals in most central and peripheral
neurons where they control the calcium (Ca2+) entry that triggers
exocytosis. CaV2.2 channels are under tight regulatory control by
many intra- and extracellular molecules. One of the best-documented
forms of regulation is inhibition by presynaptic G protein-coupled
receptors (GPCRs). In the past three decades since this was first
discovered we have learned much about inhibition of CaV2.2 by
neurotransmitters, neurohormones, and drugs, and also about the
structure, function, and binding partners of CaVs, G proteins, and
GPCRs. GPCR inhibition of CaV2.2 channels varies by GPCR-type and
by tissue. In this thesis I present data that suggest a new
perspective in understanding the diversity in coupling between
GPCRs and CaV2.2 channels: that
alternative splicing of the target
channel determines the ability of specific receptors to inhibit
Ca2+ currents. I build off of previous work from our lab showing
that
alternative splicing of a set of mutually exclusive exons in
CaV2.2 pre-mRNA controls the ability of Gi/o protein-coupled
receptors (Gi/oPCRs) to inhibit CaV2.2. I first show differential
coupling of GPCRs to splice variants of CaV2.2 (Chapter 2), then I
show that
alternative exon 18a (e18a) modulates inhibition by Gs
protein-coupled receptors (GsPCRs; Chapter 3), and finally I
present preliminary data gathered to identify the signaling cascade
between GsPCRs and e18a-containing CaV2.2 channels (Chapter 4).
Advisors/Committee Members: Lipscombe, Diane (Director), Kauer, Julie (Reader), Barnea, Gilad (Reader), Ikeda, Stephen (Reader).
Subjects/Keywords: alternative splicing
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APA (6th Edition):
Phillips, C. G. (2012). Alternative Splicing Controls G Protein Inhibition of CaV2.2
Calcium Channels. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:297699/
Chicago Manual of Style (16th Edition):
Phillips, Cecilia G. “Alternative Splicing Controls G Protein Inhibition of CaV2.2
Calcium Channels.” 2012. Doctoral Dissertation, Brown University. Accessed February 27, 2021.
https://repository.library.brown.edu/studio/item/bdr:297699/.
MLA Handbook (7th Edition):
Phillips, Cecilia G. “Alternative Splicing Controls G Protein Inhibition of CaV2.2
Calcium Channels.” 2012. Web. 27 Feb 2021.
Vancouver:
Phillips CG. Alternative Splicing Controls G Protein Inhibition of CaV2.2
Calcium Channels. [Internet] [Doctoral dissertation]. Brown University; 2012. [cited 2021 Feb 27].
Available from: https://repository.library.brown.edu/studio/item/bdr:297699/.
Council of Science Editors:
Phillips CG. Alternative Splicing Controls G Protein Inhibition of CaV2.2
Calcium Channels. [Doctoral Dissertation]. Brown University; 2012. Available from: https://repository.library.brown.edu/studio/item/bdr:297699/
3.
Allen, Summer E.
Cell-specific splicing factors that optimize calcium channel
function.
Degree: PhD, Neuroscience, 2012, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:297693/
► Alternative splicing in the nervous system is an important regulator of neuronal function. CaV2.2 calcium channels control neurotransmission and are extensively alternatively spliced in a…
(more)
▼ Alternative splicing in the nervous system is an
important regulator of neuronal function. CaV2.2 calcium channels
control neurotransmission and are extensively alternatively spliced
in a cell-type specific manner. Splice isoforms of these channels
have distinct basic biophysical properties and unique responses to
G protein-coupled receptors. RNA-binding proteins called
splicing
factors regulate the inclusion of
alternative exons. There are
several methods that can be used to identify the
splicing factors
that regulate inclusion of a particular exon. In this dissertation,
I explore the factors that regulate the inclusion of functionally
important
alternative exons within CaV2.2. In Chapter 2, I show
that Nova-2 represses inclusion of exons 31a in CaV2.1 and CaV2.2
in the central nervous system and present evidence that Nova-2
enhances inclusion of an exon which I discovered, exon 24a in
CaV2.1. In Chapter 3, I show that Fox proteins repress inclusion of
exon 18a in CaV2.2 and that this
splicing regulation controls the
voltage-independent inhibition of channel proteins by Gs-coupled
receptor agonists. In Chapter 4, I present results from minigene
and bioinformatics analyses that were used to attempt to identify
the
splicing factors that regulate the
splicing of mutually
exclusive exons 37a and 37b in CaV2.2. Inclusion of exon 37a in
CaV2.2 channels in neurons of dorsal root ganglia allows Gi/o
coupled-receptor agonists, like morphine, to inhibit CaV2.2
channels in a voltage-independent manner. Although I have yet to
identify the
splicing factors involved, I present evidence from
minigene studies that suggests a model including a repressor of
exon 37a and an enhancer of exon 37b. Bioinformatic analyses
suggest that hnRNP-A/B and hnRNP-F may regulate inclusion of these
exons. In the discussion chapter I examine how studies such
as mine
can provide important insight into cell-specific optimization of
protein function. I also discuss models of
splicing regulation and
exciting avenues for future research.
Advisors/Committee Members: Lipscombe, Diane (Director), Connors, Barry (Reader), Fairbrother, William (Reader), Hart, Anne (Reader), Eberwine, James (Reader).
Subjects/Keywords: alternative splicing
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APA ·
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APA (6th Edition):
Allen, S. E. (2012). Cell-specific splicing factors that optimize calcium channel
function. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:297693/
Chicago Manual of Style (16th Edition):
Allen, Summer E. “Cell-specific splicing factors that optimize calcium channel
function.” 2012. Doctoral Dissertation, Brown University. Accessed February 27, 2021.
https://repository.library.brown.edu/studio/item/bdr:297693/.
MLA Handbook (7th Edition):
Allen, Summer E. “Cell-specific splicing factors that optimize calcium channel
function.” 2012. Web. 27 Feb 2021.
Vancouver:
Allen SE. Cell-specific splicing factors that optimize calcium channel
function. [Internet] [Doctoral dissertation]. Brown University; 2012. [cited 2021 Feb 27].
Available from: https://repository.library.brown.edu/studio/item/bdr:297693/.
Council of Science Editors:
Allen SE. Cell-specific splicing factors that optimize calcium channel
function. [Doctoral Dissertation]. Brown University; 2012. Available from: https://repository.library.brown.edu/studio/item/bdr:297693/
University of Bath
4.
Tovar-Corona, Jaime M.
Cross-species characterisation of alternative splicing patterns.
Degree: PhD, 2014, University of Bath
URL: https://researchportal.bath.ac.uk/en/studentthesis/crossspecies-characterisation-of-alternative-splicing-patterns(80313e16-1ec3-47ab-ae0b-1fdb526f3f2f).html
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.636519
► Alternative splicing is a common post-transcriptional process in eukaryote organisms by which a single gene can produce more than one distinct transcript. First discovered in…
(more)
▼ Alternative splicing is a common post-transcriptional process in eukaryote organisms by which a single gene can produce more than one distinct transcript. First discovered in the late 1970s, alternative splicing has been the focus of intense attention after the release of the human genome draft revealed a lower than expected gene number. Almost all human protein coding genes are now known to be alternatively spliced. However, how alternative splicing in humans and other well studied model organisms compares to other less characterised taxa such as protists and fungi or what is the functional role of alternative splicing remains poorly understood. Here I analyse alternative splicing in dozens of species using millions of partial transcript sequences ESTs. By applying a transcript normalisation method I showed that alternative splicing in protists and fungi is higher than previously reported and highly variable. I further observed that in representatives of both taxa, associations with translation are overrepresented among alternatively spliced genes. However, no evidence for a relationship between alternative splicing and complex phenotypes was found. Taking human lice as a model I explored the role of alternative splicing in the evolution of phenotypic variants. I found that, despite the fact that the transcriptome profiles of head and body lice are nearly identical, there are markedly differences in alternative splicing patterns. Development related functional associations were found to be enriched among genes with body lice specific alternative splicing events but not in head lice consistent with a scenario of differential patterns of alternative splicing contributing to the phenotypic innovations as human lice adapted to life in human clothing. I further explore the functional relevance of alternative splicing and its possible role in driving genomic innovations even preceding events of gene duplication. Together the work presented show that alternative splicing is widespread among previously understudied fungi and protist species and provide insights on its role in species adaptation to novel environments in using human lice as a model.
Subjects/Keywords: 572.8; Alternative Splicing
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APA (6th Edition):
Tovar-Corona, J. M. (2014). Cross-species characterisation of alternative splicing patterns. (Doctoral Dissertation). University of Bath. Retrieved from https://researchportal.bath.ac.uk/en/studentthesis/crossspecies-characterisation-of-alternative-splicing-patterns(80313e16-1ec3-47ab-ae0b-1fdb526f3f2f).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.636519
Chicago Manual of Style (16th Edition):
Tovar-Corona, Jaime M. “Cross-species characterisation of alternative splicing patterns.” 2014. Doctoral Dissertation, University of Bath. Accessed February 27, 2021.
https://researchportal.bath.ac.uk/en/studentthesis/crossspecies-characterisation-of-alternative-splicing-patterns(80313e16-1ec3-47ab-ae0b-1fdb526f3f2f).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.636519.
MLA Handbook (7th Edition):
Tovar-Corona, Jaime M. “Cross-species characterisation of alternative splicing patterns.” 2014. Web. 27 Feb 2021.
Vancouver:
Tovar-Corona JM. Cross-species characterisation of alternative splicing patterns. [Internet] [Doctoral dissertation]. University of Bath; 2014. [cited 2021 Feb 27].
Available from: https://researchportal.bath.ac.uk/en/studentthesis/crossspecies-characterisation-of-alternative-splicing-patterns(80313e16-1ec3-47ab-ae0b-1fdb526f3f2f).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.636519.
Council of Science Editors:
Tovar-Corona JM. Cross-species characterisation of alternative splicing patterns. [Doctoral Dissertation]. University of Bath; 2014. Available from: https://researchportal.bath.ac.uk/en/studentthesis/crossspecies-characterisation-of-alternative-splicing-patterns(80313e16-1ec3-47ab-ae0b-1fdb526f3f2f).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.636519
5.
Villagra, Ulises Maximiliano Mancini.
Análise de splicing alternativo utilizando dados de sequências expressas.
Degree: PhD, Biologia (Genética), 2009, University of São Paulo
URL: http://www.teses.usp.br/teses/disponiveis/41/41131/tde-02032010-094119/
;
► O splicing alternativo é um processo pelo qual os exons de um transcrito primário são ligados de diferentes maneiras durante o processamento do RNA, levando…
(more)
▼ O splicing alternativo é um processo pelo qual os exons de um transcrito primário são ligados de diferentes maneiras durante o processamento do RNA, levando à síntese de proteínas distintas. Compreende um importante mecanismo na expressão gênica de eucariotos, responsável pelo aumento da diversidade proteômica e, portanto da capacidade codificante do genoma. Diferentes mecanismos parecem afetar a regulação do splicing alternativo, incluindo estresse metabólico. No presente estudo, foi realizada uma análise detalhada de sequências ORESTES de tecidos de cabeça e pescoço. Essa análise revelou que o ganho de sequências exônicas é mais freqüente que sua perda, e que a regra GT/AG é predominante em sítios de splicing. Nós observamos que o splicing alternativo geralmente não altera a matriz de leitura, mas pode afetar um domínio protéico e remover ou adicionar novos sítios de fosforilação e glicosilação. Elementos reguladores potenciais e elementos repetitivos foram freqüentes nas sequências alternativas e nas suas vizinhas. A expressão de isoformas de splicing potenciais foi investigada em diferentes tecidos, incluindo sob condições de estresse. Foram validados cerca de 50 eventos de splicing novos em células normais e tumorais. Diversas variantes, tais como aquelas dos genes HNRNPK, ACTN1, BAT3, CEP192, MPV17, PDK1, PRKAR1A, RAG1AP1 e TRIP6 mostraram padrões de expressão distintos em diferentes tipos celulares, em amostras normais e tumorais de pacientes com carcinoma de cabeça e pescoço e, em alguns casos, em diferentes estágios do tumor. Também foi validado um transcrito novo do gene RIPK2, responsável por codificar uma quinase de serine/treonine que ativa a via de sinalização NF-kB, e foi observada uma mudança na expressão dessa variante em resposta ao estresse térmico in vitro. Ainda não está claramente definido se o splicing alternativo é causa ou conseqüência do processo neoplásico. Nossos dados adicionam informações novas a esse tópico e fornecem alguns exemplos que evidenciam a importância do processamento do RNA na regulação da expressão gênica, tanto em condições normais como de doença.
Alternative splicing is a process by which the exons of the primary gene transcript are linked in different ways during RNA processing resulting in distinctive proteins. It is an important mechanism in eukaryotic gene expression that enhances proteome diversity and, therefore, the coding capacity of the genome. Different mechanisms seem affect alternative splicing regulation, including metabolic stresses. In the present study, a detailed informatics analysis of ORESTES sequences from head and neck tissues was performed. This in silico analysis revealed that gain of exon sequences is more frequent than exon skipping and GT/AG rule is predominant in splice sites. We observed that alternative splicing usually does not alter the reading frame but may disrupt a protein domain and remove or add new phosphorylation and glycosylation sites. Repetitive and potential regulator elements were frequent in the alternative sequences or in…
Advisors/Committee Members: Silva, Eloiza Helena Tajara da.
Subjects/Keywords: splicing alternativo; Alternative splicing; Transcriptome; Transcritoma
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APA ·
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MLA ·
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Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Villagra, U. M. M. (2009). Análise de splicing alternativo utilizando dados de sequências expressas. (Doctoral Dissertation). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/41/41131/tde-02032010-094119/ ;
Chicago Manual of Style (16th Edition):
Villagra, Ulises Maximiliano Mancini. “Análise de splicing alternativo utilizando dados de sequências expressas.” 2009. Doctoral Dissertation, University of São Paulo. Accessed February 27, 2021.
http://www.teses.usp.br/teses/disponiveis/41/41131/tde-02032010-094119/ ;.
MLA Handbook (7th Edition):
Villagra, Ulises Maximiliano Mancini. “Análise de splicing alternativo utilizando dados de sequências expressas.” 2009. Web. 27 Feb 2021.
Vancouver:
Villagra UMM. Análise de splicing alternativo utilizando dados de sequências expressas. [Internet] [Doctoral dissertation]. University of São Paulo; 2009. [cited 2021 Feb 27].
Available from: http://www.teses.usp.br/teses/disponiveis/41/41131/tde-02032010-094119/ ;.
Council of Science Editors:
Villagra UMM. Análise de splicing alternativo utilizando dados de sequências expressas. [Doctoral Dissertation]. University of São Paulo; 2009. Available from: http://www.teses.usp.br/teses/disponiveis/41/41131/tde-02032010-094119/ ;
Uniwersytet im. Adama Mickiewicza w Poznaniu
6.
Kalak, Małgorzata Maria.
Udział miRNA w regulacji alternatywnego splicingu u roślin
.
Degree: 2013, Uniwersytet im. Adama Mickiewicza w Poznaniu
URL: http://hdl.handle.net/10593/8972
► W czasie splicingu alternatywnego z pre-mRNA pojedynczego genu może powstać wiele różnych wariantów mRNA. Powstające w wyniku expresji genu różne formy mRNA mogą kodować funkcjonalnie…
(more)
▼ W czasie splicingu alternatywnego z pre-mRNA pojedynczego genu może powstać wiele różnych wariantów mRNA. Powstające w wyniku expresji genu różne formy mRNA mogą kodować funkcjonalnie odmienne białka i wpływać na wielkość i kompleksowość proteomu. Eksperymenty wykonane w ramach pracy doktorskiej wskazują, że białka kompleksu CBC oddziałują z białkiem SERRATE. Ponadto, analiza RT-PCR ujawniła, że AtSE (podobnie do AtCBC) bierze udział w regulacji splicingu alternatywnego, głównie przez wpływ na wybór alternatywnego miejsca splicingowego typu 5’SS w pierwszym intronie. Białka AtSE i AtCBC współpracują ze sobą, gdyż wiele zmian profilu splicingu alternatywnego obserwowanych w mutancie se-1 jest wspólna ze zmianami w mutantach cbc. W kolejnym etapie badań oceniono wpływ uszkodzenia ścieżki dojrzewania miRNA na profil splicingu alternatywnego wybranych genów. W tym celu analizę RT-PCR rozszerzono o badanie splicingu alternatywnego w innych niż se-1 mutantach genów kodujących białka zaangażowane w biogenezę miRNA – hyl1-2 oraz dcl1-7. Zaobserwowano, że dla kilku genów zmiany w profilu splicingu alternatywnego są wspólne dla wszystkich analizowanych mutantów, co może wskazywać na istnienie nowego mechanizmu regulacji splicingu alternatywnego u roślin - poprzez udział miRNA lub innych sRNA. Dla jednego ze zmienionych genów w wyniku analizy bioinformatycznej wyłoniono cząsteczkę sRNA pochodzącą z Gln-tRNATTG, która może hybrydyzować do najdłuższej izoformy mRNA czynnika splicingowego AtRS31 i naznaczać ją do degradacji. W analizowanych mutantach poziom tRF-
AS jest obniżony, podczas gdy poziom najdłuższej izoformy genu AtRS31 wzrasta. Na podstawie uzyskanych wyników potwierdzono hipotezę o udziale sRNA w regulacji splicingu alternatywnego u roślin. Dalsza analiza bioinformatyczna ujawniła istnienie większej ilości cząsteczek sRNA , które powstają z tRNA. Obecność in vivo kilku wyselekcjonowanych cząsteczek potwierdzono poprzez hybrydyzację typu Northern blot.
Advisors/Committee Members: Jarmołowski, Artur. Promotor (advisor).
Subjects/Keywords: splicing alternatywny;
alternative splicing;
miRNA;
Arabidopsis
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APA ·
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MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kalak, M. M. (2013). Udział miRNA w regulacji alternatywnego splicingu u roślin
. (Doctoral Dissertation). Uniwersytet im. Adama Mickiewicza w Poznaniu. Retrieved from http://hdl.handle.net/10593/8972
Chicago Manual of Style (16th Edition):
Kalak, Małgorzata Maria. “Udział miRNA w regulacji alternatywnego splicingu u roślin
.” 2013. Doctoral Dissertation, Uniwersytet im. Adama Mickiewicza w Poznaniu. Accessed February 27, 2021.
http://hdl.handle.net/10593/8972.
MLA Handbook (7th Edition):
Kalak, Małgorzata Maria. “Udział miRNA w regulacji alternatywnego splicingu u roślin
.” 2013. Web. 27 Feb 2021.
Vancouver:
Kalak MM. Udział miRNA w regulacji alternatywnego splicingu u roślin
. [Internet] [Doctoral dissertation]. Uniwersytet im. Adama Mickiewicza w Poznaniu; 2013. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/10593/8972.
Council of Science Editors:
Kalak MM. Udział miRNA w regulacji alternatywnego splicingu u roślin
. [Doctoral Dissertation]. Uniwersytet im. Adama Mickiewicza w Poznaniu; 2013. Available from: http://hdl.handle.net/10593/8972
University of Auckland
7.
Dickson, James Michael Jeremy.
Characterization of calpain 3 transcripts in mammalian cells : expression of alternatively-spliced variants in non-muscle cell types.
Degree: 2008, University of Auckland
URL: http://hdl.handle.net/2292/2490
► An investigation of the expression profile of mRNA encoding Calpain 3, the causative agent in the inherited human muscular disease Limb Girdle Muscular Dystrophy Type…
(more)
▼ An investigation of the expression profile of mRNA encoding Calpain 3, the causative agent in the inherited human muscular disease Limb Girdle Muscular Dystrophy Type 2A, was conducted in two representative mammalian species, human and mouse. Transcripts encoding Calpain 3 were identified from mammalian tissues other than skeletal muscle. In human Peripheral Blood Mononuclear Cells (PBMCs) these transcripts were identified in both the T-cell and B-cell compartments and in a number of human blood cell lines representing different haematopoietic lineages. Calpain 3 transcripts encoding the murine homologue were also described from mouse PBMCs and from murine tissues involved in haematopoiesis. In addition to the confirmation of Calpain 3 expression in non-skeletal muscle tissues in both these species, transcripts were identified with precise and defined deletions, which mapped to known exon-exon boundaries in the Calpain 3 gene from both species. These deletions constituted the removal by
alternative splicing of skeletal muscle-specific components of the Calpain 3 protein known to regulate its function in this tissue.
Monoclonal antibodies to the Calpain 3 protein were used to confirm the presence of Calpain 3 protein in non-skeletal muscle tissues of both human and mouse. In humans the expression of Calpain 3 protein was confirmed in PBMCs and in the mouse, Calpain 3 expression was confirmed in tissues of the haematopoietic compartment. In both species the Calpain 3 protein expressed correlated with translation from a transcript lacking the skeletal muscle-specific components generated by
alternative splicing. An attempt was made using a Yeast Two Hybrid assay to identify potential regulatory molecules of Calpain 3 in human PBMCs, but without a definitive candidate molecule being found.
A developmental model of muscle differentiation (murine C2C12 myoblast cells) was used to ascertain the expression profile of Calpain 3 in the early stages of myofibrillogenesis. Using Quantitative Real Time PCR the expression profile of Calpain 3 was assessed in differentiating C2C12 cells. These results showed that the absolute levels of Calpain 3 transcription were elevated during differentiation and that a temporal Calpain 3 isoform shift occurred during this process. This temporal shift in expression was from transcripts having identical deletions to those seen in the haematopoietic tissues, to full length transcripts representative of skeletal muscle-specific Calpain 3.
The identification of Calpain 3 expression outside skeletal muscle tissue is novel and the isoforms expressed in these tissues are structurally more analogous to the ubiquitously expressed calpains. This has implications for LGMD2A where a loss of function of Calpain 3 in non-skeletal muscle tissue could be compensated for by the ubiquitous calpains, thus explaining the lack of any non-muscle tissue pathology in LGMD2A patients.
Advisors/Committee Members: Associate Professor Clive Evans.
Subjects/Keywords: Mammalian; Calpain 3; Alternative-splicing
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APA (6th Edition):
Dickson, J. M. J. (2008). Characterization of calpain 3 transcripts in mammalian cells : expression of alternatively-spliced variants in non-muscle cell types. (Doctoral Dissertation). University of Auckland. Retrieved from http://hdl.handle.net/2292/2490
Chicago Manual of Style (16th Edition):
Dickson, James Michael Jeremy. “Characterization of calpain 3 transcripts in mammalian cells : expression of alternatively-spliced variants in non-muscle cell types.” 2008. Doctoral Dissertation, University of Auckland. Accessed February 27, 2021.
http://hdl.handle.net/2292/2490.
MLA Handbook (7th Edition):
Dickson, James Michael Jeremy. “Characterization of calpain 3 transcripts in mammalian cells : expression of alternatively-spliced variants in non-muscle cell types.” 2008. Web. 27 Feb 2021.
Vancouver:
Dickson JMJ. Characterization of calpain 3 transcripts in mammalian cells : expression of alternatively-spliced variants in non-muscle cell types. [Internet] [Doctoral dissertation]. University of Auckland; 2008. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/2292/2490.
Council of Science Editors:
Dickson JMJ. Characterization of calpain 3 transcripts in mammalian cells : expression of alternatively-spliced variants in non-muscle cell types. [Doctoral Dissertation]. University of Auckland; 2008. Available from: http://hdl.handle.net/2292/2490
8.
山本, 真照.
ヒトの遺伝子における選択的スプライシングによる膜タンパク質の機能構造の変化 : alternative splicing of transmembrane proteins in human genes; ヒト ノ イデンシ ニ オケル センタクテキ スプライシング ニ ヨル マク タンパクシツ ノ キノウ コウゾウ ノ ヘンカ.
Degree: Nara Institute of Science and Technology / 奈良先端科学技術大学院大学
URL: http://hdl.handle.net/10061/1918
Subjects/Keywords: alternative splicing
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APA (6th Edition):
山本, . (n.d.). ヒトの遺伝子における選択的スプライシングによる膜タンパク質の機能構造の変化 : alternative splicing of transmembrane proteins in human genes; ヒト ノ イデンシ ニ オケル センタクテキ スプライシング ニ ヨル マク タンパクシツ ノ キノウ コウゾウ ノ ヘンカ. (Thesis). Nara Institute of Science and Technology / 奈良先端科学技術大学院大学. Retrieved from http://hdl.handle.net/10061/1918
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
山本, 真照. “ヒトの遺伝子における選択的スプライシングによる膜タンパク質の機能構造の変化 : alternative splicing of transmembrane proteins in human genes; ヒト ノ イデンシ ニ オケル センタクテキ スプライシング ニ ヨル マク タンパクシツ ノ キノウ コウゾウ ノ ヘンカ.” Thesis, Nara Institute of Science and Technology / 奈良先端科学技術大学院大学. Accessed February 27, 2021.
http://hdl.handle.net/10061/1918.
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
山本, 真照. “ヒトの遺伝子における選択的スプライシングによる膜タンパク質の機能構造の変化 : alternative splicing of transmembrane proteins in human genes; ヒト ノ イデンシ ニ オケル センタクテキ スプライシング ニ ヨル マク タンパクシツ ノ キノウ コウゾウ ノ ヘンカ.” Web. 27 Feb 2021.
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Vancouver:
山本 . ヒトの遺伝子における選択的スプライシングによる膜タンパク質の機能構造の変化 : alternative splicing of transmembrane proteins in human genes; ヒト ノ イデンシ ニ オケル センタクテキ スプライシング ニ ヨル マク タンパクシツ ノ キノウ コウゾウ ノ ヘンカ. [Internet] [Thesis]. Nara Institute of Science and Technology / 奈良先端科学技術大学院大学; [cited 2021 Feb 27].
Available from: http://hdl.handle.net/10061/1918.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.
Council of Science Editors:
山本 . ヒトの遺伝子における選択的スプライシングによる膜タンパク質の機能構造の変化 : alternative splicing of transmembrane proteins in human genes; ヒト ノ イデンシ ニ オケル センタクテキ スプライシング ニ ヨル マク タンパクシツ ノ キノウ コウゾウ ノ ヘンカ. [Thesis]. Nara Institute of Science and Technology / 奈良先端科学技術大学院大学; Available from: http://hdl.handle.net/10061/1918
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.
Cornell University
9.
Awan, Ali.
Discovering Alternative Splicing Of Deeply Conserved Exons And Characterizing The Intronome In The Unicellular Yeast S. Pombe Using Lariat Sequencing.
Degree: PhD, Genetics, 2013, Cornell University
URL: http://hdl.handle.net/1813/34200
► Alternative splicing is a potent regulator of gene expression that vastly increases proteomic diversity in multi-cellular eukaryotes. Although it is widespread in vertebrates, little is…
(more)
▼ Alternative splicing is a potent regulator of gene expression that vastly increases proteomic diversity in multi-cellular eukaryotes. Although it is widespread in vertebrates, little is known about the evolutionary origins of this process owing in part to the absence of phylogenetically conserved events that cross major eukaryotic clades. The unicellular fission yeast, Schizosaccharomyces pombe, is an organism evolutionarily distant from mammals that nonetheless shares many of the hallmarks of the major mammalian
alternative splicing form, exon skipping. Further, S. pombe is a highly genetically tractable organism that has been considered
as an attractive potential model system in which to study exon skipping. However, evidence of exon skipping from RNA-seq studies in S. pombe has remained elusive. To better search for such evidence I have developed a novel lariat sequencing approach that offers high sensitivity for detecting
splicing events, and applied it to study
splicing in S. pombe. Using this approach, I discovered multiple examples of exon skipping, several of which involve exons that are conserved with dozens of animals, plants, other fungi and even protists. Strikingly, some of the specific
alternative splicing patterns found in S. pombe are identical in mammals. In addition, I discovered hundreds of novel
splicing events, many of which occur in genes that were thought to be intronless. Finally, I present only the second large-scale map of the intronic branch point sequences in any organism, allowing me to test a prediction about differences in splice site recognition in introns from non-coding regions versus those that separate protein-coding exons.
Advisors/Committee Members: Pleiss, Jeffrey A. (chair), Lis, John T (committee member), Alani, Eric (committee member).
Subjects/Keywords: Alternative Splicing; Sequencing; pombe
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APA (6th Edition):
Awan, A. (2013). Discovering Alternative Splicing Of Deeply Conserved Exons And Characterizing The Intronome In The Unicellular Yeast S. Pombe Using Lariat Sequencing. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/34200
Chicago Manual of Style (16th Edition):
Awan, Ali. “Discovering Alternative Splicing Of Deeply Conserved Exons And Characterizing The Intronome In The Unicellular Yeast S. Pombe Using Lariat Sequencing.” 2013. Doctoral Dissertation, Cornell University. Accessed February 27, 2021.
http://hdl.handle.net/1813/34200.
MLA Handbook (7th Edition):
Awan, Ali. “Discovering Alternative Splicing Of Deeply Conserved Exons And Characterizing The Intronome In The Unicellular Yeast S. Pombe Using Lariat Sequencing.” 2013. Web. 27 Feb 2021.
Vancouver:
Awan A. Discovering Alternative Splicing Of Deeply Conserved Exons And Characterizing The Intronome In The Unicellular Yeast S. Pombe Using Lariat Sequencing. [Internet] [Doctoral dissertation]. Cornell University; 2013. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/1813/34200.
Council of Science Editors:
Awan A. Discovering Alternative Splicing Of Deeply Conserved Exons And Characterizing The Intronome In The Unicellular Yeast S. Pombe Using Lariat Sequencing. [Doctoral Dissertation]. Cornell University; 2013. Available from: http://hdl.handle.net/1813/34200
North Carolina State University
10.
Zhao, Sihui.
Analysis of Cis-acting Regulatory Motifs Involved in Alternative Splicing.
Degree: PhD, Statistics, 2009, North Carolina State University
URL: http://www.lib.ncsu.edu/resolver/1840.16/5374
► Alternative splicing is an important posttranscriptional process in eukaryotes. It dramatically expands the proteome and contributes essentially to the regulation of gene expression. Cis-acting regulatory…
(more)
▼ Alternative splicing is an important posttranscriptional process in eukaryotes. It dramatically expands the proteome and contributes essentially to the regulation of gene expression. Cis-acting regulatory motifs play a pivotal role in the regulation of
alternative splicing. Many human diseases involved with aberrant (
alternative)
splicing are caused by mutations of
splicing regulatory motifs. However, due to the short, degenerate and context-dependent nature, the prediction of cis-acting
splicing motifs is a very challenging task.
In this dissertation, we focus on discovery of
splicing signals from sequences. This may help to reveal the integrated
splicing code and to understand the regulation of gene expression in the resolution of exon level.
In chapter one, we review the up-to-date research development in
alternative splicing and its regulation,
as well
as the experimental and computational approaches in genome-wide
alternative splicing analysis.
We describe a large-scale data analysis experiment to discover
AS motifs in chapter two. We applied a computational framework to re-analyze a dataset containing about 3,000 cassette exons and skipping rates for regulatory motifs. The
alternative spliced events were clustered by their expression profiles to find co-regulated genes. Rather than using a fixed cutoff
as cluster boundary, we used systematic sampling to sample sequence clusters and eliminated redundant motifs predicted from overlapping clusters. We conclude that these predicted motifs may be promising candidates responsible for
AS regulation by comparison to known motifs and by positional bias.
In chapter three, we describe a new approach to discover short and degenerate
AS motifs. We implemented a two-step approach incorporating skipping rates in motif discovery. In the simulation study, we show that this approach is especially suitable to discover short and highly degenerate motifs. Analysis of cassette exons in Central Nervous System tissues produced 15 motifs which are associated with the variation of skipping rates. We discover that Nova and hnRNP A1 binding sites are involved with
AS regulation,
as well
as about ten novel motifs. Moreover, co-operation between predicted motifs are also revealed.
In chapter four, we give the present status of SPRED, a database of cis-acting regulatory
splicing elements. The motifs in SPRED are compiled from literature. They are all experimentally validated. The web interface is publically accessible and accompanied with query and similarity search tools. The goal of SPRED is to provide a comprehensive motif dictionary to facilitate the research in
AS and its regulation.
Finally, we give the conclusions in chapter five. We also give the perspective for future study and briefly review the potential challenge.
Advisors/Committee Members: Steffen Heber, Committee Chair (advisor), Zhao-Bang Zeng, Committee Co-Chair (advisor), David Bird, Committee Member (advisor), Hao Zhang, Committee Member (advisor).
Subjects/Keywords: alternative splicing; motif discovery
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APA (6th Edition):
Zhao, S. (2009). Analysis of Cis-acting Regulatory Motifs Involved in Alternative Splicing. (Doctoral Dissertation). North Carolina State University. Retrieved from http://www.lib.ncsu.edu/resolver/1840.16/5374
Chicago Manual of Style (16th Edition):
Zhao, Sihui. “Analysis of Cis-acting Regulatory Motifs Involved in Alternative Splicing.” 2009. Doctoral Dissertation, North Carolina State University. Accessed February 27, 2021.
http://www.lib.ncsu.edu/resolver/1840.16/5374.
MLA Handbook (7th Edition):
Zhao, Sihui. “Analysis of Cis-acting Regulatory Motifs Involved in Alternative Splicing.” 2009. Web. 27 Feb 2021.
Vancouver:
Zhao S. Analysis of Cis-acting Regulatory Motifs Involved in Alternative Splicing. [Internet] [Doctoral dissertation]. North Carolina State University; 2009. [cited 2021 Feb 27].
Available from: http://www.lib.ncsu.edu/resolver/1840.16/5374.
Council of Science Editors:
Zhao S. Analysis of Cis-acting Regulatory Motifs Involved in Alternative Splicing. [Doctoral Dissertation]. North Carolina State University; 2009. Available from: http://www.lib.ncsu.edu/resolver/1840.16/5374
University of Connecticut
11.
Guerrette, Thomas A.
Alternative Splicing Factor CELF4 is Implicated in Regulation of Ganglion Cell Differentiation During Murine Retinal Development.
Degree: MS, Physiology and Neurobiology, 2012, University of Connecticut
URL: https://opencommons.uconn.edu/gs_theses/277
► CELF4 is an RNA-binding protein believed to play a role as an alternative splicing factor that regulates the inclusion or exclusion of RNA into…
(more)
▼ CELF4 is an RNA-binding protein believed to play a role
as an
alternative splicing factor that regulates the inclusion or exclusion of RNA into the mature messengerRNA. Mice deficient for this gene die postnally. Heterozygous CELF4 knockout mice have a complex seizure phenotype. Murine CELF4 expression is restricted to the central nervous system. Here we characterize its expression in murine retinal tissue and comment on the role it plays in mammalian retinal development. It has been discovered that mice deficient for this gene have developmental defects in the retina. An enlarged ganglion cell layer in CELF4 mutants is observed at P0. Immunostaining shows that cells in the ganglion cell layer of CELF4 mutants at P0 are not staining for mature ganglion cells. We posit that loss of CELF4 inhibits ganglion cell differentiation and maturation in the retina disturbing normal development of the eye.
Advisors/Committee Members: Anastasios Tzingounis, David Goldhamer, Charles Giardina, Rahul Kanadia.
Subjects/Keywords: Alternative Splicing; Neurobiology; Retina
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APA (6th Edition):
Guerrette, T. A. (2012). Alternative Splicing Factor CELF4 is Implicated in Regulation of Ganglion Cell Differentiation During Murine Retinal Development. (Masters Thesis). University of Connecticut. Retrieved from https://opencommons.uconn.edu/gs_theses/277
Chicago Manual of Style (16th Edition):
Guerrette, Thomas A. “Alternative Splicing Factor CELF4 is Implicated in Regulation of Ganglion Cell Differentiation During Murine Retinal Development.” 2012. Masters Thesis, University of Connecticut. Accessed February 27, 2021.
https://opencommons.uconn.edu/gs_theses/277.
MLA Handbook (7th Edition):
Guerrette, Thomas A. “Alternative Splicing Factor CELF4 is Implicated in Regulation of Ganglion Cell Differentiation During Murine Retinal Development.” 2012. Web. 27 Feb 2021.
Vancouver:
Guerrette TA. Alternative Splicing Factor CELF4 is Implicated in Regulation of Ganglion Cell Differentiation During Murine Retinal Development. [Internet] [Masters thesis]. University of Connecticut; 2012. [cited 2021 Feb 27].
Available from: https://opencommons.uconn.edu/gs_theses/277.
Council of Science Editors:
Guerrette TA. Alternative Splicing Factor CELF4 is Implicated in Regulation of Ganglion Cell Differentiation During Murine Retinal Development. [Masters Thesis]. University of Connecticut; 2012. Available from: https://opencommons.uconn.edu/gs_theses/277
University of Edinburgh
12.
Smith, Paul Hugh.
Dscam gene expression in invertebrate immunity : alternative splicing in response to diverse pathogens.
Degree: PhD, 2012, University of Edinburgh
URL: http://hdl.handle.net/1842/9888
► Invertebrates show enhanced immunity and even specific primed immunity in response to repeat infections, analogous to vertebrate adaptive immunity. Little is known of the mechanism…
(more)
▼ Invertebrates show enhanced immunity and even specific primed immunity in response to repeat infections, analogous to vertebrate adaptive immunity. Little is known of the mechanism for this phenomenon, or which molecules are involved. A candidate gene for the underlying mechanism for a pathogen-specific response in invertebrate immunity is Down syndrome cell adhesion molecule (Dscam). Dscam can produce thousands of different protein isoforms through the mutually exclusive splicing of many exon variants contained within variable regions of the gene. It is an important receptor of the invertebrate nervous system but has been implicated in having a role in immunity. Dscam has been shown to be involved in phagocytosis across members of the Pancrustacea, and it has been reported to respond in a pathogen-specific manner in mosquitoes and crayfish. In this thesis, I have investigated the splicing of Dscam in response to diverse pathogens in different host species. In the Anopheles mosquito, I cloned and sequenced a fragment of Dscam spanning across two of its variable exon regions to enable me to detect mutually exclusively splice variants and their associations in different treatments (Chapter 2). I discovered that the expression diversity of the hypervariable Dscam is higher in parasite-exposed mosquitoes. In Chapter 3, I extended the study to the more experimentally amenable Drosophila fruit fly. A new Illumina-based sequencing assay was developed and implemented to examine more closely Dscam expression in response to diverse pathogens. The new method successfully quantified non-random expression of Dscam variable exons 4 and 6. I also describe a small but detectable effect of pathogen-exposure on the expression of Dscam exon 4 variants. In Chapter 4, I expanded the work of Chapter 3 to study tissue-specific Dscam expression in response to well-characterised immune elicitors of Drosophila. I describe how exon 4 variants were expressed in a tissue-specific manner, but not exon 6 variants. I also found a small exon 4-by-tissue-by-pathogen effect, which although detectable, did not dominate over the tissue effects. Finally, in Chapter 5, I turned to the crustacean, Daphnia, to study Dscam expression in a natural host-parasite interaction and in a clonal organism. I describe the non-random expression of exons 4 and 6, and another small effect of pathogen-exposure on the expression of Dscam exon 4. My work aimed to further investigate the putative pathogen-specific alternative splicing of the hypervariable Dscam receptor. The data presented quantified the constitutive expression of Dscam exons 4 and 6 in different pancrustacean species. The data also suggest that infection-responsive splicing of Dscam may occur but that effects are small, and may be diluted within the background of the highly important Dscam expression of the nervous system if they exist at all. The study supports the high-throughput sequencing method for future studies of alternative splicing and Dscam expression.
Subjects/Keywords: 572.8; Dscam; alternative splicing
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APA ·
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APA (6th Edition):
Smith, P. H. (2012). Dscam gene expression in invertebrate immunity : alternative splicing in response to diverse pathogens. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/9888
Chicago Manual of Style (16th Edition):
Smith, Paul Hugh. “Dscam gene expression in invertebrate immunity : alternative splicing in response to diverse pathogens.” 2012. Doctoral Dissertation, University of Edinburgh. Accessed February 27, 2021.
http://hdl.handle.net/1842/9888.
MLA Handbook (7th Edition):
Smith, Paul Hugh. “Dscam gene expression in invertebrate immunity : alternative splicing in response to diverse pathogens.” 2012. Web. 27 Feb 2021.
Vancouver:
Smith PH. Dscam gene expression in invertebrate immunity : alternative splicing in response to diverse pathogens. [Internet] [Doctoral dissertation]. University of Edinburgh; 2012. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/1842/9888.
Council of Science Editors:
Smith PH. Dscam gene expression in invertebrate immunity : alternative splicing in response to diverse pathogens. [Doctoral Dissertation]. University of Edinburgh; 2012. Available from: http://hdl.handle.net/1842/9888
13.
Jabre, I.
Understanding the epigenetics of alternative splicing in Arabidopsis thaliana.
Degree: PhD, 2019, Canterbury Christ Church University
URL: https://repository.canterbury.ac.uk/item/8qv53/understanding-the-epigenetics-of-alternative-splicing-in-arabidopsis-thaliana
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.801664
► Being sessile and photosynthetic necessitates that plants must have a certain degree of predictability for ambient conditions during the daily cycles to maximise efficiency and…
(more)
▼ Being sessile and photosynthetic necessitates that plants must have a certain degree of predictability for ambient conditions during the daily cycles to maximise efficiency and survival. However, subtle or sudden changes in weather conditions alongside different growth and developmental phases necessitate that plants must continuously monitor different environmental cues and synchronise them with their physiology and metabolism in a time, growth phase and development-stage dependent manner. Plants use complex gene regulatory mechanisms to overcome environmental challenges. Alternative splicing (AS) of pre-mRNAs, a process that generates two or more transcripts from multi-exon genes, adds another layer of complexity to gene regulatory mechanisms to modulate transcriptome diversity in a tissue- and condition-dependent manner. In mammals, mounting evidence indicates that chromatin structure can regulate co-transcriptional AS. Recent evidence supports co-transcriptional regulation of AS in plants, but how dynamic changes in the chromatin influence the AS process upon cold stress remains poorly understood and is the subject of this study. In order to answer this question, four approaches were followed in parallel; (1) Arabidopsis thaliana (Arabidopsis) plants with identical DNA sequence but differential DNA methylation and nucleosome occupancy (Ctrl and AzadC plants with wild type DNA methylation and hypomethylation, respectively) were developed to perform (2) RNA sequencing (RNA-seq) and (3) Micrococcal Nuclease sequencing (MNase-seq) for Ctrl and AzadC grown at 22 °C and at 4 °C as cold treatment for 24 hours, and (4) whole genome bisulphite sequencing (WGBS) for AzadC grown at 22 °C and at 4 °C as cold treatment for 24 hours. This strategy allowed us to understand how epigenetic variations between AzadC treatment derived lines and Ctrl plants affect AS under cold conditions, without the confounding effects of sequence variation. Interestingly, RNA-seq, MNase-seq, and WGBS show a strong reprogramming of AS patterns upon cold stress associated with changes in epigenetic features (i.e. DNA methylation and nucleosome occupancy). To my knowledge, this is the first study in Arabidopsis that demonstrates that changes in transcriptional and AS patterns coincide with genome-wide changes in nucleosome occupancy and DNA methylation patterns upon temperature shift.
Subjects/Keywords: Arabidopsis thaliana; Epigenetics; Alternative splicing
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APA (6th Edition):
Jabre, I. (2019). Understanding the epigenetics of alternative splicing in Arabidopsis thaliana. (Doctoral Dissertation). Canterbury Christ Church University. Retrieved from https://repository.canterbury.ac.uk/item/8qv53/understanding-the-epigenetics-of-alternative-splicing-in-arabidopsis-thaliana ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.801664
Chicago Manual of Style (16th Edition):
Jabre, I. “Understanding the epigenetics of alternative splicing in Arabidopsis thaliana.” 2019. Doctoral Dissertation, Canterbury Christ Church University. Accessed February 27, 2021.
https://repository.canterbury.ac.uk/item/8qv53/understanding-the-epigenetics-of-alternative-splicing-in-arabidopsis-thaliana ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.801664.
MLA Handbook (7th Edition):
Jabre, I. “Understanding the epigenetics of alternative splicing in Arabidopsis thaliana.” 2019. Web. 27 Feb 2021.
Vancouver:
Jabre I. Understanding the epigenetics of alternative splicing in Arabidopsis thaliana. [Internet] [Doctoral dissertation]. Canterbury Christ Church University; 2019. [cited 2021 Feb 27].
Available from: https://repository.canterbury.ac.uk/item/8qv53/understanding-the-epigenetics-of-alternative-splicing-in-arabidopsis-thaliana ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.801664.
Council of Science Editors:
Jabre I. Understanding the epigenetics of alternative splicing in Arabidopsis thaliana. [Doctoral Dissertation]. Canterbury Christ Church University; 2019. Available from: https://repository.canterbury.ac.uk/item/8qv53/understanding-the-epigenetics-of-alternative-splicing-in-arabidopsis-thaliana ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.801664
University of New South Wales
14.
Kim, Youngsoo.
Identification of TRPC3c ion channels in the brain: molecular physiology and region-specific regulation.
Degree: Medical Sciences, 2015, University of New South Wales
URL: http://handle.unsw.edu.au/1959.4/54248
;
https://unsworks.unsw.edu.au/fapi/datastream/unsworks:13713/SOURCE02?view=true
► Canonical transient receptor potential 3 (TRPC3) channels are nonselective cation channels from the TRPC family that are particularly important in Ca2+ homeostasis and signalling in…
(more)
▼ Canonical transient receptor potential 3 (TRPC3) channels are nonselective cation channels from the TRPC family that are particularly important in Ca2+ homeostasis and signalling in neurons. These channels have multiple modes of activation, via a G-protein coupled receptor (GPCR) – phospholipase C (PLC) – diacylglycerol (DAG) pathway,
as well
as via intracellular store depletion and coupling to the inositol triphosphate (IP¬3) receptor. The TRPC3 channels are highly expressed in the brain and have diverse functions. In the cerebellum, TRPC3 has been shown to mediate neuroprotection or neurotoxicity, growth cone guidance, and neurotransmission related to motor coordination. This study focusses on the discovery and functional characterisation of a novel TRPC3 subunit splice variant, designated
as TRPC3c. TRPC3c is formed by omission of a small exon (exon 9) which consists of 84 bases thatcodes for 28 amino acids. This exon codes for a significant portion of a regulatory domain known
as the calmodulin - inositol triphosphate (IP3) receptor binding (CIRB) domain in the C-terminus. The TRPC3c splice variant is shown here to be widely expressed throughout the brain in various mammalian species including, mouse, rat, guinea pig and human. TRPC3c showed the highest expression level in the cerebellum in all these species. Functional characterisation of the recombinant TRPC3c channels by means of Ca2+ imaging and electrophysiology showed that this isoform has very high activity, with an increased channel opening rate compared to the formerly discovered TRPC3b isoform (wild-type). Our data suggests that this increased activity may be attributed to reduced sensitivity to intracellular [Ca2+], possibly due to altered interaction with intracellular regulators of the channels such
as calmodulin. Given the high expression of the TRPC3c isoform in the cerebellum and its unusually high channel activity, it is likely that TRPC3c contributes significantly to Ca2+ and Na+ entry. TRPC3c may therefore have a crucial role in several cellular processes, including neuronal growth, survival, death, and neurotransmission.
Advisors/Committee Members: Housley, Gary, Medical Sciences, Faculty of Medicine, UNSW, Moorhouse, Andrew, Medical Sciences, Faculty of Medicine, UNSW, Bertrand, Paul, School of Medical Sciences, RMIT.
Subjects/Keywords: Cerebellum; TRPC3; Alternative splicing
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APA (6th Edition):
Kim, Y. (2015). Identification of TRPC3c ion channels in the brain: molecular physiology and region-specific regulation. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/54248 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:13713/SOURCE02?view=true
Chicago Manual of Style (16th Edition):
Kim, Youngsoo. “Identification of TRPC3c ion channels in the brain: molecular physiology and region-specific regulation.” 2015. Doctoral Dissertation, University of New South Wales. Accessed February 27, 2021.
http://handle.unsw.edu.au/1959.4/54248 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:13713/SOURCE02?view=true.
MLA Handbook (7th Edition):
Kim, Youngsoo. “Identification of TRPC3c ion channels in the brain: molecular physiology and region-specific regulation.” 2015. Web. 27 Feb 2021.
Vancouver:
Kim Y. Identification of TRPC3c ion channels in the brain: molecular physiology and region-specific regulation. [Internet] [Doctoral dissertation]. University of New South Wales; 2015. [cited 2021 Feb 27].
Available from: http://handle.unsw.edu.au/1959.4/54248 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:13713/SOURCE02?view=true.
Council of Science Editors:
Kim Y. Identification of TRPC3c ion channels in the brain: molecular physiology and region-specific regulation. [Doctoral Dissertation]. University of New South Wales; 2015. Available from: http://handle.unsw.edu.au/1959.4/54248 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:13713/SOURCE02?view=true
King Abdullah University of Science and Technology
15.
Kababji, Ahad M.
Targeted mutagenesis and functional analysis of CWC25 Splicing Factor in Rice via CRISPR/Cas9.
Degree: Biological and Environmental Sciences and Engineering (BESE) Division, 2019, King Abdullah University of Science and Technology
URL: http://hdl.handle.net/10754/660281
► Pre-mRNA splicing is the most critical process in gene expression regulation across eukaryotic species. This reaction is carried out by the spliceosome, a large, dynamic,…
(more)
▼ Pre-mRNA
splicing is the most critical process in gene expression regulation across eukaryotic species. This reaction is carried out by the spliceosome, a large, dynamic, and well-organized ribonucleoprotein complex. The spliceosome is composed of five major small nuclear RNAs and an excessive number of associated protein factors. Many protein
splicing factors bind and release during
splicing to assist the assembly and the modulation of many RNA structures and proteins within the spliceosome. CWC25 is a
splicing protein factor that functions in modulating the conformational structure of the spliceosome at the first transesterification reaction. CWC25 binds with its N-terminus to the major groove of the catalytic spliceosome triggering the spliceosome activity. Here, we employed CRISPR/Cas9 genome engineering system for targeted mutagenesis to generate CWC25 functional knock-out mutants to understand its molecular function, contribution to
splicing regulation and implication in fine-tuning responses to abiotic stress in rice. Our genotyping analysis of the OsCWC25 locus revealed the presence of two mono-allelic and 18 bi-allelic mutant lines. Phenotypic analysis of these mutants, including germination and root inhibition assays, showed that the cwc25 mutants are oversensitive to abiotic stresses such
as ABA and salinity. Our data demonstrate that CWC25 plays an important role in regulating plant responses to abiotic stresses.
Advisors/Committee Members: Mahfouz, Magdy M. (advisor), Blilou, Ikram (committee member), Ghaffour, NorEddine (committee member).
Subjects/Keywords: Splicing; Alternative Splicing; Splicing Factors; CWC25; CRISPR/Cas9; Spliceosome
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APA (6th Edition):
Kababji, A. M. (2019). Targeted mutagenesis and functional analysis of CWC25 Splicing Factor in Rice via CRISPR/Cas9. (Thesis). King Abdullah University of Science and Technology. Retrieved from http://hdl.handle.net/10754/660281
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Kababji, Ahad M. “Targeted mutagenesis and functional analysis of CWC25 Splicing Factor in Rice via CRISPR/Cas9.” 2019. Thesis, King Abdullah University of Science and Technology. Accessed February 27, 2021.
http://hdl.handle.net/10754/660281.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Kababji, Ahad M. “Targeted mutagenesis and functional analysis of CWC25 Splicing Factor in Rice via CRISPR/Cas9.” 2019. Web. 27 Feb 2021.
Vancouver:
Kababji AM. Targeted mutagenesis and functional analysis of CWC25 Splicing Factor in Rice via CRISPR/Cas9. [Internet] [Thesis]. King Abdullah University of Science and Technology; 2019. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/10754/660281.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Kababji AM. Targeted mutagenesis and functional analysis of CWC25 Splicing Factor in Rice via CRISPR/Cas9. [Thesis]. King Abdullah University of Science and Technology; 2019. Available from: http://hdl.handle.net/10754/660281
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
KTH
16.
Linder, Johannes.
Modeling the intronic regulation of Alternative Splicing using Deep Convolutional Neural Nets.
Degree: Computer Science and Communication (CSC), 2015, KTH
URL: http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-172327
► This paper investigates the use of deep Convolutional Neural Networks for modeling the intronic regulation of Alternative Splicing on the basis of DNA sequence.…
(more)
▼ This paper investigates the use of deep Convolutional Neural Networks for modeling the intronic regulation of Alternative Splicing on the basis of DNA sequence. By training the CNN on massively parallel synthetic DNA libraries of Alternative 5'-splicing and Alternatively Skipped exon events, the model is capable of predicting the relative abundance of alternatively spliced mRNA isoforms on held-out library data to a very high accuracy (R2 = 0.77 for Alt. 5'-splicing). Furthermore, the CNN is shown to generalize alternative splicing across cell lines efficiently. The Convolutional Neural Net is tested against a Logistic regression model and the results show that while prediction accuracy on the synthetic library is notably higher compared to the LR model, the CNN is worse at generalizing to new intronic contexts. Tests on non-synthetic human SNP genes suggest the CNN is dependent on the relative position of the intronic region it was trained for, a problem which is alleviated with LR. The increased library prediction accuracy of the CNN compared to Logistic regression is concluded to come from the non-linearity introduced by the deep layer architecture. It adds the capacity to model complex regulatory interactions and combinatorial RBP effects which studies have shown largely affect alternative splicing. However, the architecture makes interpreting the CNN hard, as the regulatory interactions are encoded deep within the layers. Nevertheless, high-performance modeling of alternative splicing using CNNs may still prove useful in numerous Synthetic biology applications, for example to model differentially spliced genes as is done in this paper.
Den här uppsatsen undersöker hur djupa neurala nätverk baserade på faltning ("Convolutions") kan användas för att modellera den introniska regleringen av Alternativ Splicing med endast DNA-sekvensen som indata. Nätverket tränas på ett massivt parallelt bibliotek av syntetiskt DNA innehållandes Alternativa Splicing-event där delar av de introniska regionerna har randomiserats. Uppsatsen visar att nätverksarkitekturen kan förutspå den relativa mängden alternativt splicat RNA till en mycket hög noggrannhet inom det syntetiska biblioteket. Modellen generaliserar även alternativ splicing mellan mänskliga celltyper väl. Hursomhelst, tester på icke-syntetiska mänskliga gener med SNP-mutationer visar att nätverkets prestanda försämras när den introniska region som används som indata flyttas i jämförelse till den relativa position som modellen tränats på. Uppsatsen jämför modellen med Logistic regression och drar slutsatsen att nätverkets förbättrade prestanda grundar sig i dess förmåga att modellera icke-linjära beroenden i datan. Detta medför dock svårigheter i att tolka vad modellen faktiskt lärt sig, eftersom interaktionen mellan reglerande element är inbäddat i nätverkslagren. Trots det kan högpresterande modellering av alternativ splicing med hjälp av neurala nät vara användbart, exempelvis inom Syntetisk biologi där modellen kan användas för att kontrollera…
Subjects/Keywords: Machine Learning; Deep Learning; CNN; CNNs; Convolutional Neural Networks; Convolutional Neural Nets; Neural Networks; Neural Nets; Synthetic Biology; Alternative Splicing; AS; Splicing; DNA Regulation; Synthetic DNA; Massively Parallel Library; Maskinlärning; CNN; CNNs; Convolutional Neural Networks; Convolutional Neural Nets; Faltning; Neurala Nätverk; Neurala Nät; Syntetisk Biologi; Alternativ Splicing; Splicing; AS; DNA; Massivt Parallellt Bibliotek; Syntetiskt DNA; Computer Sciences; Datavetenskap (datalogi)
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Linder, J. (2015). Modeling the intronic regulation of Alternative Splicing using Deep Convolutional Neural Nets. (Thesis). KTH. Retrieved from http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-172327
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Linder, Johannes. “Modeling the intronic regulation of Alternative Splicing using Deep Convolutional Neural Nets.” 2015. Thesis, KTH. Accessed February 27, 2021.
http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-172327.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Linder, Johannes. “Modeling the intronic regulation of Alternative Splicing using Deep Convolutional Neural Nets.” 2015. Web. 27 Feb 2021.
Vancouver:
Linder J. Modeling the intronic regulation of Alternative Splicing using Deep Convolutional Neural Nets. [Internet] [Thesis]. KTH; 2015. [cited 2021 Feb 27].
Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-172327.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Linder J. Modeling the intronic regulation of Alternative Splicing using Deep Convolutional Neural Nets. [Thesis]. KTH; 2015. Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-172327
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of California – Berkeley
17.
Brooks, Angela Norie.
RNA Splicing Regulation in Drosophila melanogaster.
Degree: Molecular & Cell Biology, 2011, University of California – Berkeley
URL: http://www.escholarship.org/uc/item/26r3r0cq
► A majority of metazoan genes contain introns in their primary transcripts (pre-mRNA) that require removal by the spliceosome – a cellular complex composed of protein and…
(more)
▼ A majority of metazoan genes contain introns in their primary transcripts (pre-mRNA) that require removal by the spliceosome – a cellular complex composed of protein and RNA. Upon removal of introns from the primary transcript, the remaining exonic portion of the transcript is spliced together. It is essential to remove the correct intronic portion of a primary transcript in order to produce the desired product, typically a protein-coding mRNA. Pre-mRNAs are alternatively spliced when different intron boundaries are used by the spliceosome, thus creating different mRNA products. Alternative splicing allows for an additional step of gene regulation by producing transcript isoforms that can be differentially processed in a particular tissue or developmental time point. Alternative splicing is primarily regulated by RNA binding proteins that bind to pre-mRNA and act to recruit or inhibit the spliceosome at specific splice sites. A central aim of this work is to gain a better understanding of splicing regulation by the identification and characterization of protein regulators of splicing and cis-acting splicing regulatory sequences in the model organism, Drosophila melanogaster. To identify splicing regulatory elements, many previous studies in vertebrate genomes have used computational methods. In collaboration with Anna I. Podgornaia, I applied such an approach to predict splicing regulatory elements in Drosophila melanogaster and compared them with elements found in vertebrates. I identified 330 putative splicing enhancer sequences enriched near weak 5' and 3' splice sites of constitutively spliced introns. I found that a significant proportion (58%) of D. melanogaster enhancers were previously reported as splicing enhancers in vertebrates. To provide additional evidence for the function of the intronic splicing enhancers (ISEs), I identified intronic hexamers significantly enriched within sequences phylogenetically conserved among 15 insect species. This analysis uncovered 73 putative ISEs that are also enriched in conserved regions of the D. melanogaster genome. The functions of nine enhancer sequences were verified in a heterologous splicing reporter by Julie L. Aspden, demonstrating that these sequences are sufficient to enhance splicing in vivo. Taken together, these data identify a set of predicted positive-acting splicing regulatory motifs in the Drosophila genome and highlight those regulatory sequences that are present in distant metazoan genomes. To identify and characterize splicing regulators, collaborators and I have combined RNAi and RNA-Seq to identify exons that are regulated by 58 known or putative splicing regulators. To identify and quantify alternative splicing events from RNA-Seq data, I developed the JuncBASE (Junction Based Analysis of Splicing Events) software package. For a pilot study, I identified 404 splicing events significantly affected upon depletion of…
Subjects/Keywords: Bioinformatics; Genetics; alternative splicing; development; Drosophila; RNA-Seq; splicing regulation; splicing regulatory enhancers
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APA ·
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Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Brooks, A. N. (2011). RNA Splicing Regulation in Drosophila melanogaster. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/26r3r0cq
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Brooks, Angela Norie. “RNA Splicing Regulation in Drosophila melanogaster.” 2011. Thesis, University of California – Berkeley. Accessed February 27, 2021.
http://www.escholarship.org/uc/item/26r3r0cq.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Brooks, Angela Norie. “RNA Splicing Regulation in Drosophila melanogaster.” 2011. Web. 27 Feb 2021.
Vancouver:
Brooks AN. RNA Splicing Regulation in Drosophila melanogaster. [Internet] [Thesis]. University of California – Berkeley; 2011. [cited 2021 Feb 27].
Available from: http://www.escholarship.org/uc/item/26r3r0cq.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Brooks AN. RNA Splicing Regulation in Drosophila melanogaster. [Thesis]. University of California – Berkeley; 2011. Available from: http://www.escholarship.org/uc/item/26r3r0cq
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Technical University of Lisbon
18.
Nunes, Vera Alexandra Sacramento.
Functional insights into the plant-specific SR45 splicing factor.
Degree: 2014, Technical University of Lisbon
URL: https://www.rcaap.pt/detail.jsp?id=oai:www.repository.utl.pt:10400.5/8260
► Mestrado em Engenharia Agronómica - Instituto Superior de Agronomia
Alternative splicing is a post-transcriptional regulatory mechanism that generates transcriptome and proteome diversity. The SR protein…
(more)
▼ Mestrado em Engenharia Agronómica - Instituto Superior de Agronomia
Alternative splicing is a post-transcriptional regulatory mechanism that generates transcriptome and proteome diversity. The SR protein family of splicing regulators is essential for the execution and regulation of both constitutive and alternative pre-mRNA splicing. The SR-related protein SR45 is an Arabidopsis bona fide splicing factor that plays a key role in plant development as well as in sugar and abscisic acid (ABA) signaling during early seedling development. The Arabidopsis 5PTase13, belonging to a group of inositol phosphatases involved in plant growth, development and stress responses, is a splicing target of SR45 previously implicated in hormonal and light signaling pathways.
The 5PTase13 gene is alternatively spliced, generating two isoforms shown here to be ubiquitously expressed in Arabidopsis. The 5PTase13 loss-of-function mutant we isolated exhibits shorter roots when grown under low light conditions. Moreover, overexpression of either the 5PTase13.1 or the 5PTase13.2 isoforms in the sr45-1 background enhances the glucose hypersensitivity during early seedling development conferred by the sr45-1 mutation. Finally, confocal microscopy data suggests that both 5PTase13 isoforms are located in the cytoplasm, with 5PTase13.1 appearing mostly associated with the plasma membrane. This work provides new insight into the in vivo roles of the SR45 splicing factor and its functional connections to the 5PTase13 phosphatase
Advisors/Committee Members: Santos, Paula Duque Magalhães, Carvalho, Raquel Fonseca, Amâncio, Sara Barros Queiróz.
Subjects/Keywords: 5PTase13; ABA; alternative splicing; Arabidopsis; glucose; SR45
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APA (6th Edition):
Nunes, V. A. S. (2014). Functional insights into the plant-specific SR45 splicing factor. (Thesis). Technical University of Lisbon. Retrieved from https://www.rcaap.pt/detail.jsp?id=oai:www.repository.utl.pt:10400.5/8260
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Nunes, Vera Alexandra Sacramento. “Functional insights into the plant-specific SR45 splicing factor.” 2014. Thesis, Technical University of Lisbon. Accessed February 27, 2021.
https://www.rcaap.pt/detail.jsp?id=oai:www.repository.utl.pt:10400.5/8260.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Nunes, Vera Alexandra Sacramento. “Functional insights into the plant-specific SR45 splicing factor.” 2014. Web. 27 Feb 2021.
Vancouver:
Nunes VAS. Functional insights into the plant-specific SR45 splicing factor. [Internet] [Thesis]. Technical University of Lisbon; 2014. [cited 2021 Feb 27].
Available from: https://www.rcaap.pt/detail.jsp?id=oai:www.repository.utl.pt:10400.5/8260.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Nunes VAS. Functional insights into the plant-specific SR45 splicing factor. [Thesis]. Technical University of Lisbon; 2014. Available from: https://www.rcaap.pt/detail.jsp?id=oai:www.repository.utl.pt:10400.5/8260
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of California – Irvine
19.
Berg, Bethany Larson.
Assessing the impact of potential alternative splicing on phenotypic differences among patients with mitochondrial complex I deficiency.
Degree: Genetic Counseling, 2017, University of California – Irvine
URL: http://www.escholarship.org/uc/item/4s07r545
► With the onset of clinical whole exome sequencing, novel gene mutations have been identified in numerous patients with previously undiagnosed diseases, including those with mitochondrial…
(more)
▼ With the onset of clinical whole exome sequencing, novel gene mutations have been identified in numerous patients with previously undiagnosed diseases, including those with mitochondrial disease of unknown etiology. Complex I deficiency is one of the most common mitochondrial disorders and is both clinically and genetically heterogeneous. Many mutations within the nuclear and mitochondrial genomes have been thoroughly studied for their impact on complex I function based on deleterious alterations in protein function and prevalence among affected individuals. However, many mutations, including splicing mutations, require further analyses of mRNA transcripts in order to understand the impact on disease pathology and potential phenotypic differences.This study was designed to assess the potential affect of alternative splicing among three patients (two siblings and one unrelated patient) with complex I deficiency and compound heterozygous mutations in NUBPL. Each of them share the same branch-site mutation in NUBPL, c.815-27T>C, but have differences in disease severity. Using primers designed to separately encompass this mutation as well as a different splice mutation in the unrelated patient (c.693+1 G>A), reverse transcription polymerase chain reaction (RT-PCR) was performed on RNA from patient fibroblasts. Gel electrophoresis demonstrated alternative splicing occurring in all three patients following RT-PCR with the branch site mutation primers. In addition, whole exome data from the two siblings was re-analyzed and potential modifier genes affecting NUBPL were studied. Our results support the importance of investigating potentially pathogenic mutations using RNA studies given that alternative splicing can significantly impact phenotypic expression across different tissues and different individuals.
Subjects/Keywords: Genetics; alternative splicing; Complex I deficiency; NUBPL
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APA (6th Edition):
Berg, B. L. (2017). Assessing the impact of potential alternative splicing on phenotypic differences among patients with mitochondrial complex I deficiency. (Thesis). University of California – Irvine. Retrieved from http://www.escholarship.org/uc/item/4s07r545
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Berg, Bethany Larson. “Assessing the impact of potential alternative splicing on phenotypic differences among patients with mitochondrial complex I deficiency.” 2017. Thesis, University of California – Irvine. Accessed February 27, 2021.
http://www.escholarship.org/uc/item/4s07r545.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Berg, Bethany Larson. “Assessing the impact of potential alternative splicing on phenotypic differences among patients with mitochondrial complex I deficiency.” 2017. Web. 27 Feb 2021.
Vancouver:
Berg BL. Assessing the impact of potential alternative splicing on phenotypic differences among patients with mitochondrial complex I deficiency. [Internet] [Thesis]. University of California – Irvine; 2017. [cited 2021 Feb 27].
Available from: http://www.escholarship.org/uc/item/4s07r545.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Berg BL. Assessing the impact of potential alternative splicing on phenotypic differences among patients with mitochondrial complex I deficiency. [Thesis]. University of California – Irvine; 2017. Available from: http://www.escholarship.org/uc/item/4s07r545
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
UCLA
20.
Silva, Oscar.
Discs Large Homolog 1: Molecular Scaffolds Guiding T Cell Activation and Effector Function.
Degree: Microbiology, Immunology, & Molecular Genetics, 2013, UCLA
URL: http://www.escholarship.org/uc/item/55k9p6qd
► Discs large homolog 1 (Dlgh1) is a scaffold protein that couples T cell receptor (TCR) engagement to signal transduction and cytoskeletal reorganization. Specifically, Dlgh1 directs…
(more)
▼ Discs large homolog 1 (Dlgh1) is a scaffold protein that couples T cell receptor (TCR) engagement to signal transduction and cytoskeletal reorganization. Specifically, Dlgh1 directs Lck and ZAP70 kinase activity toward the selective activation of mitogen-activated protein kinase p38 and transcription factor NFAT. In addition, Dlgh1 controls actin polymerization, TCR and lipid raft clustering, and MTOC positioning during TCR engagement. The ability to selectively activate, integrate and tune these pathways may allow Dlgh1 to promote discrete cellular responses including: T cell differentiation, proliferation, cytokine production, cell-mediated cytotoxicity and memory generation. Therefore, understanding how Dlgh1 channels proximal TCR signals to specific downstream pathways to trigger distinct cellular responses in T cells requires 1) an understanding of how Dlgh1 is regulated by post-transcriptional and post-translational modifications, and 2) the development of a suitable Dlgh1 knockout (Dlgh1 KO) mouse model to assess Dlgh1 function in vivo.Alternative splicing and phosphorylation of Dlgh1 are post-transcriptional and post-translational modifications that regulate Dlgh1 localization, expression and function. We found that alternative splicing of Dlgh1 in CD8+ effector T cells resulted in the expression of two distinct Dlgh1 protein variants: Dlgh1 AB and Dlgh1 B. Further, these two Dlgh1 variants served as molecular conduits to drive distinct cytotoxic T lymphocyte (CTL) responses. While both Dlgh1 AB and Dlgh1 B promoted p38-independent lytic factor degranulation, which required actin polymerization and the cytoskeletal regulator WASp, only Dlgh1 AB coupled Lck to p38-dependent production of proinflammatory cytokines. In addition, this CTL effector function was found to require Lck-mediated Dlgh1 AB tyrosine phosphorylation at tyrosine 222, suggesting that Dlgh1 AB tyrosine phosphorylation may provide a unique mechanism to specifically regulate p38-dependent functions in T cells. Lastly, we found that acute inducible knockout of Dlgh1 in mature peripheral T cells prevented optimal T cell activation and effector function in CD8+ T cells, while knockout of Dlgh1 in the germline or developing T cells had little or no effect on T cell function. Together, these data suggests that the developmental timing of Dlgh1 ablation may be critical for observing Dlgh1-dependent functional effects. We propose that T lymphocytes construct functionally unique Dlgh1 AB/Lck/p38 and Dlgh1/WASp complexes as a mechanism to specifically direct proximal TCR signals towards distinct cellular responses.
Subjects/Keywords: Immunology; alternative splicing; Dlgh1; T cell signaling
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APA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Silva, O. (2013). Discs Large Homolog 1: Molecular Scaffolds Guiding T Cell Activation and Effector Function. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/55k9p6qd
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Silva, Oscar. “Discs Large Homolog 1: Molecular Scaffolds Guiding T Cell Activation and Effector Function.” 2013. Thesis, UCLA. Accessed February 27, 2021.
http://www.escholarship.org/uc/item/55k9p6qd.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Silva, Oscar. “Discs Large Homolog 1: Molecular Scaffolds Guiding T Cell Activation and Effector Function.” 2013. Web. 27 Feb 2021.
Vancouver:
Silva O. Discs Large Homolog 1: Molecular Scaffolds Guiding T Cell Activation and Effector Function. [Internet] [Thesis]. UCLA; 2013. [cited 2021 Feb 27].
Available from: http://www.escholarship.org/uc/item/55k9p6qd.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Silva O. Discs Large Homolog 1: Molecular Scaffolds Guiding T Cell Activation and Effector Function. [Thesis]. UCLA; 2013. Available from: http://www.escholarship.org/uc/item/55k9p6qd
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Toronto
21.
Wainberg, Michael.
Does Conservation Account for Splicing Patterns?.
Degree: 2015, University of Toronto
URL: http://hdl.handle.net/1807/70705
► A computational model is presented that predicts absolute (though not tissue-differential) percent-spliced-in of cassette exons more accurately than previous models. Nearly identical performance is achieved…
(more)
▼ A computational model is presented that predicts absolute (though not tissue-differential) percent-spliced-in of cassette exons more accurately than previous models. Nearly identical performance is achieved using only the conservation score (mammalian phastCons) of each splice junction normalized by average conservation over 100 bp of the corresponding flanking intron. Evidence is provided that splicing regulation occurs predominantly in these averaging regions, and that conserved elements there are splicing regulators, predominantly inhibitors. Among conserved cassette exons, increased conservation of flanking introns is associated with reduced inclusion, suggesting one mechanism for the evolutionary transition from constitutive to alternative splicing is the emergence of cis-acting splicing inhibitors. A new definition is proposed for intronic splicing regulatory elements (ISREs) that is independent of conservation. Most ISREs do not match known binding sites or splicing factors despite being predictive of percent-spliced-in, suggesting the existence of novel RNA-binding proteins and novel splicing roles for known RNA-binding proteins.
M.A.S.
Advisors/Committee Members: Frey, Brendan, Electrical and Computer Engineering.
Subjects/Keywords: alternative splicing; evolutionary conservation; neural networks; 0715
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APA (6th Edition):
Wainberg, M. (2015). Does Conservation Account for Splicing Patterns?. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/70705
Chicago Manual of Style (16th Edition):
Wainberg, Michael. “Does Conservation Account for Splicing Patterns?.” 2015. Masters Thesis, University of Toronto. Accessed February 27, 2021.
http://hdl.handle.net/1807/70705.
MLA Handbook (7th Edition):
Wainberg, Michael. “Does Conservation Account for Splicing Patterns?.” 2015. Web. 27 Feb 2021.
Vancouver:
Wainberg M. Does Conservation Account for Splicing Patterns?. [Internet] [Masters thesis]. University of Toronto; 2015. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/1807/70705.
Council of Science Editors:
Wainberg M. Does Conservation Account for Splicing Patterns?. [Masters Thesis]. University of Toronto; 2015. Available from: http://hdl.handle.net/1807/70705
University of Texas Southwestern Medical Center
22.
Wong, Sze.
Regulation of Human Telomerase Alternative Splicing.
Degree: 2014, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/3574
► Telomerase adds TTAGGG repeats onto chromosome ends (telomeres). Since telomerase is expressed in ~90% of all human cancer cells while being absent in most somatic…
(more)
▼ Telomerase adds TTAGGG repeats onto chromosome ends (telomeres). Since telomerase is expressed in ~90% of all human cancer cells while being absent in most somatic tissues, telomerase is an almost universal cancer therapeutic target. Yet, the clinical application of an effective telomerase inhibitor is still lacking. The pre-mRNA of the catalytic subunit of human telomerase (hTERT) may be alternatively spliced into 22 different isoforms. Only a small fraction of hTERT transcripts are spliced into the full length isoform, the form capable of being translated into function hTERT with reverse transcriptase activity. If telomerase activity is partially regulated at the level of RNA
splicing, then telomerase activity may be modulated to increase the amount of nonfunctional transcripts and decrease the amount of full-length hTERT and this would be a novel anti-cancer therapeutic approach.
A hTERT minigene was created to understand the cis-regulatory elements governing hTERT
splicing. A 1.1kb region of 38 bp repeats (block 6) ~2 kb from the exon/intron junctions is essential for the exclusion of exons 7 and 8. Block 6 repeats suggested that RNA:RNA pairing may regulate
splicing of hTERT. Mutations within the repeat sequence that abolish exon skipping were corrected by compensatory mutations in the pre-mRNA. To identify trans-acting regulators of hTERT
alternative splicing, the minigene was modified into a dual-luciferase reporter for a selected 528 RNA-binding proteins/
splicing factors siRNA screen. Our initial validation focused on 45 factors with enzymatic activity and resulted in CDC-Like Kinase 1 (CLK-1)
as a potential hTERT
splicing modulator. Knock-down of CLK-1 altered hTERT
splicing, resulting in reduction in telomerase activity and telomere shortening. CLK-1 belongs to the Clk family of dual-specificity nuclear kinases that can auto-phosphorylate SR proteins. TG003, a chemical CLK-1/4 inhibitor, results in less full length hTERT
splicing and a decrease in cancer cell telomerase activity. This approach provides a platform to identify additional hTERT
splicing regulators that may be suitable drug targets to increase or decrease telomerase activity. Altogether, these results demonstrate the potential of manipulating hTERT
splicing as a target for both chemotherapy and regenerative medicine.
Advisors/Committee Members: Fontoura, Beatriz, Wright, Woodring E., Shay, Jerry W., Conrad, Nicholas, Martinez, Elisabeth.
Subjects/Keywords: Alternative Splicing; Protein-Serine-Threonine Kinases; Telomerase
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APA (6th Edition):
Wong, S. (2014). Regulation of Human Telomerase Alternative Splicing. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/3574
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Wong, Sze. “Regulation of Human Telomerase Alternative Splicing.” 2014. Thesis, University of Texas Southwestern Medical Center. Accessed February 27, 2021.
http://hdl.handle.net/2152.5/3574.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Wong, Sze. “Regulation of Human Telomerase Alternative Splicing.” 2014. Web. 27 Feb 2021.
Vancouver:
Wong S. Regulation of Human Telomerase Alternative Splicing. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2014. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/2152.5/3574.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Wong S. Regulation of Human Telomerase Alternative Splicing. [Thesis]. University of Texas Southwestern Medical Center; 2014. Available from: http://hdl.handle.net/2152.5/3574
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Ottawa
23.
Rakopoulos, Patricia.
Deciphering the Role of MEF2D Splice Forms During Skeletal Muscle Differentiation
.
Degree: 2011, University of Ottawa
URL: http://hdl.handle.net/10393/20022
► Members of the Mef2 transcription factor family are extensively studied within the muscle field for their ability to cooperate with the myogenic regulatory factors MyoD…
(more)
▼ Members of the Mef2 transcription factor family are extensively studied within the muscle field for their ability to cooperate with the myogenic regulatory factors MyoD and myogenin during muscle differentiation. Although it is known that Mef2 pre-mRNAs undergo alternative splicing, the different splice forms have not been functionally annotated. In this thesis, my studies aimed to characterize three Mef2D splice forms: MEF2Dα'β, MEF2Dαβ, MEF2Dαø. Our results show that MEF2D splice forms can be differentially phosphorylated by p38 MAPK and PKA in vitro. Gene expression analysis using cell lines over-expressing each Mef2D splice form suggests that they can differentially activate desmin, myosin heavy chain and myogenin expression. Mass spectrometry analyses from our pull-down assays reveal known and novel MEF2D binding partners. Our work suggests that Mef2D splice forms have overlapping but distinct roles and provides new insight into the importance of Mef2D alternative splicing during skeletal myogenesis.
Subjects/Keywords: Myogenesis;
Alternative splicing;
Mef2;
Muscle differentiation
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APA (6th Edition):
Rakopoulos, P. (2011). Deciphering the Role of MEF2D Splice Forms During Skeletal Muscle Differentiation
. (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/20022
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Rakopoulos, Patricia. “Deciphering the Role of MEF2D Splice Forms During Skeletal Muscle Differentiation
.” 2011. Thesis, University of Ottawa. Accessed February 27, 2021.
http://hdl.handle.net/10393/20022.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Rakopoulos, Patricia. “Deciphering the Role of MEF2D Splice Forms During Skeletal Muscle Differentiation
.” 2011. Web. 27 Feb 2021.
Vancouver:
Rakopoulos P. Deciphering the Role of MEF2D Splice Forms During Skeletal Muscle Differentiation
. [Internet] [Thesis]. University of Ottawa; 2011. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/10393/20022.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Rakopoulos P. Deciphering the Role of MEF2D Splice Forms During Skeletal Muscle Differentiation
. [Thesis]. University of Ottawa; 2011. Available from: http://hdl.handle.net/10393/20022
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Colorado State University
24.
Link, Alicia.
Alternative splicing and its regulatory mechanisms in photosynthetic eukaryotes.
Degree: MS(M.S.), Biology, 2011, Colorado State University
URL: http://hdl.handle.net/10217/70809
► In recent years, alternative splicing (AS) of pre-mRNAs, which generates multiple transcripts from a single gene, has emerged as an important process in general proteome…
(more)
▼ In recent years,
alternative splicing (
AS) of pre-mRNAs, which generates multiple transcripts from a single gene, has emerged
as an important process in general proteome diversity and in regulatory gene expression in multicellular eukaryotes. In Arabidopsis over 40% of intron-containing genes are alternatively spliced. However, mechanisms by which
AS is regulated in plants are not fully understood, primarily due to the lack of an in vitro
splicing system derived from plants. Furthermore, the extent of
AS in simple unicellular photosynthetic eukaryotes from which plants have evolved is also not known. My research addresses these two attributes of
splicing in plants. In Part 1 of my thesis, I have investigated an aspect of
AS regulation in plants. We have previously shown that an SR-related
splicing regulator called SR45 regulates
AS of pre-mRNAs in Arabidopsis by altering splice site selection (Ali et al. 2007). In this work using bimolecular fluorescent complements, I have demonstrated that SR45 interacts with U2AF35, an important spliceosomal protein involved in 3' splice site selection in plant cells. This interaction takes place in the nucleus, specifically in the subnuclear domains called speckles, which are known to contain
splicing regulators and other proteins involved in transcription. My work has shown that SR45 interacts with both paralogs of U2AF35 and I mapped the domains in SR45 that are involved in its interaction with U2AF35. In addition, my studies have revealed interaction of the paralogs
as hetero- and homodimers. Interestingly, U2AF35 was found to interact with U1-70K, a key protein involved in 5' splice site selection. Based on this work and previous work in our laboratory, a model is proposed that explains the role of SR45 in splice site selection. In the second part of my work I studied the extent of
alternative splicing (
AS) in the unicellular green alga Chlamydomonas, that shares a common ancestor with land plants. In collaboration with Dr. Asa Ben Hur's lab, we have performed a comprehensive analysis of
AS in Chlamydomonas reinhardtii using both computational and experimental methods. Our results show that
AS is common in Chlamydomonas, but its extent is less than what is observed in land plants. However, the relative frequency of different
splicing events in Chlamydomonas is very similar to higher plants. We have found that a large number of genes undergo
alternative splicing, and together with the simplicity of the system and the use of available molecular and genetic tools. This organism is an experimental system to investigate the mechanisms involved in
alternative splicing. To further validate predicted splice variants, we performed extensive analysis of
AS for two genes, which not only confirmed predictions but also revealed novel splice variants, suggesting that the extent of
AS is higher than we predicted.
AS can also play a role in the regulation of gene expression through processes such
as regulated unproductive
splicing and translation (RUST) that involves nonsense-mediated decay…
Advisors/Committee Members: Reddy, A. S. N. (advisor), Stack, Stephen (committee member), Lapitan, Nora (committee member).
Subjects/Keywords: algae; alternative splicing; NMD; SR45; U2AFs; Chlamydomonas
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Manager
APA (6th Edition):
Link, A. (2011). Alternative splicing and its regulatory mechanisms in photosynthetic eukaryotes. (Masters Thesis). Colorado State University. Retrieved from http://hdl.handle.net/10217/70809
Chicago Manual of Style (16th Edition):
Link, Alicia. “Alternative splicing and its regulatory mechanisms in photosynthetic eukaryotes.” 2011. Masters Thesis, Colorado State University. Accessed February 27, 2021.
http://hdl.handle.net/10217/70809.
MLA Handbook (7th Edition):
Link, Alicia. “Alternative splicing and its regulatory mechanisms in photosynthetic eukaryotes.” 2011. Web. 27 Feb 2021.
Vancouver:
Link A. Alternative splicing and its regulatory mechanisms in photosynthetic eukaryotes. [Internet] [Masters thesis]. Colorado State University; 2011. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/10217/70809.
Council of Science Editors:
Link A. Alternative splicing and its regulatory mechanisms in photosynthetic eukaryotes. [Masters Thesis]. Colorado State University; 2011. Available from: http://hdl.handle.net/10217/70809
University of Manitoba
25.
Lin, Junjun.
Molecular Regulation of a Novel Pro-Survival Bnip3 Spliced Variant NIPLET in Cardiac Myocytes Functionally Couples ER and Mitochondria.
Degree: Physiology and Pathophysiology, 2015, University of Manitoba
URL: http://hdl.handle.net/1993/31215
► Abstract Alternative splicing provides a versatile mechanism by which cells can generate proteins with different or even antagonistic properties. Herein we describe a novel splice…
(more)
▼ Abstract
Alternative splicing provides a versatile mechanism by which cells can generate proteins with different or even antagonistic properties. Herein we describe a novel splice variant of the hypoxia-inducible death gene Bnip3. Sequence analysis of the new Bnip3 protein revealed an N-terminus that was identical to Bnip3 but contained an Endoplasmic reticulum (ER) retention motif within the C-terminus, therefore we designated the new Bnip3 isoform NIPLET for (Nip-Like ER Target). While Bnip3 was predominately localized to mitochondria and promoted mitochondrial perturbations and cell death, NIPLET was preferentially localized to the ER and opposed the cytotoxic actions of Bnip3. Interestingly, NIPLET suppressed mitochondrial injury from Bnip3 activation and mitochondrial permeability transition pore opening by a mechanism dependent upon the dynamin motor protein Mitofusin-2 (MFN2). Notably, mutations of NIPLET within the critical ER retention motif rendered NIPLET defective for interacting with MFN2 and suppressed necrosis induced by Bnip3 or hypoxia. Hence, our findings reveal a novel signaling pathway that functionally couples ER and mitochondria for cell survival to a mechanism that is mutually dependent and obligatorily linked to a novel BNIP3 protein in cardiac myocytes.
Advisors/Committee Members: Kirshenbaum, Lorrie A. (Physiology and Pathophysiology) (supervisor), Singal, Pawan (Physiology and Pathophysiology).
Subjects/Keywords: Alternative Splicing; Bnip3; Mitochondria; ER; MFN2
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APA (6th Edition):
Lin, J. (2015). Molecular Regulation of a Novel Pro-Survival Bnip3 Spliced Variant NIPLET in Cardiac Myocytes Functionally Couples ER and Mitochondria. (Masters Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/31215
Chicago Manual of Style (16th Edition):
Lin, Junjun. “Molecular Regulation of a Novel Pro-Survival Bnip3 Spliced Variant NIPLET in Cardiac Myocytes Functionally Couples ER and Mitochondria.” 2015. Masters Thesis, University of Manitoba. Accessed February 27, 2021.
http://hdl.handle.net/1993/31215.
MLA Handbook (7th Edition):
Lin, Junjun. “Molecular Regulation of a Novel Pro-Survival Bnip3 Spliced Variant NIPLET in Cardiac Myocytes Functionally Couples ER and Mitochondria.” 2015. Web. 27 Feb 2021.
Vancouver:
Lin J. Molecular Regulation of a Novel Pro-Survival Bnip3 Spliced Variant NIPLET in Cardiac Myocytes Functionally Couples ER and Mitochondria. [Internet] [Masters thesis]. University of Manitoba; 2015. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/1993/31215.
Council of Science Editors:
Lin J. Molecular Regulation of a Novel Pro-Survival Bnip3 Spliced Variant NIPLET in Cardiac Myocytes Functionally Couples ER and Mitochondria. [Masters Thesis]. University of Manitoba; 2015. Available from: http://hdl.handle.net/1993/31215
University of Edinburgh
26.
McMahon, Aoife Christina.
Examination of multiple SynGAP isoforms in mammalian central neurons.
Degree: PhD, 2011, University of Edinburgh
URL: http://hdl.handle.net/1842/5621
► The ability of neurons to dynamically regulate their response to changing inputs is essential for the correct development and function of a nervous system capable…
(more)
▼ The ability of neurons to dynamically regulate their response to changing inputs is essential for the correct development and function of a nervous system capable of learning and memory. The post synaptic compartment of excitatory synapses contains a dense proteinaceous complex of molecules that link excitatory glutamatergic neurotransmission to downstream signalling pathways that ultimately result in modification of the synapse. One of the most abundant of such postsynaptic signalling molecules, synaptic GTPase activation protein, SynGAP, represents a key signalling link between the activation of the NMDA sensitive glutamate receptor to outcomes such as the structural rearrangement of synaptic sites and altered synaptic content of AMPA type glutamate receptors, molecular processes that underly learning and memory. The primary finding of this thesis is that different isoforms of SynGAP, which varies at it N terminus through alternative transcription start sites and at its C terminus through alternative splicing, can differentially affect the function of the synapse. Using primary murine neuronal cultures we show that despite being crucial for the survival of the mouse the absence of SynGAP does not effect mean dendritic spine morphology and density or miniature excitiatory post synaptic currents under a range of experimental conditions (days in vitro 10 – 14, with and without serum, high and low cell plating density). In order to examine the effects of different SynGAP isoforms we cloned two full length transcripts (SynGAP A-alpha-2 and SynGAP Ealpha- 1) which were used to construct a range of isoforms. Whole cell patch clamping of SynGAP transfected neurons revealed that the post synaptic expression of SynGAPs which terminate as an alpha-1 isoform can lead to the elimination of mEPSCs, while isoforms that terminate as an alpha-2 isoform can lead to synaptic strengthening. The magnitude of the effect in both cases is determined by the identity of the N terminus of the protein; SynGAP A-alpha-1 has the largest synaptic weakening effect and SynGAP B-and C alpha-2 strenghten the synapse. The changes in miniature electrophysiological properties are not mirrored by changes in dendritic spine morphology, whole cell AMPA/NMDA currents, or synaptic responsiveness to stimulation suggesting an undefined novel mechanism of action. SynGAPs A, B and C appear to be under the control of different promoters which are differentially regulated by development and synaptic activity, thus the differential function of SynGAP N and C terminal combinations could play a part in the activity dependent regulation of synaptic strength.
Subjects/Keywords: 612.8; SynGAP; synapse; alternative splicing; neuroscience; isoforms
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APA ·
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Manager
APA (6th Edition):
McMahon, A. C. (2011). Examination of multiple SynGAP isoforms in mammalian central neurons. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/5621
Chicago Manual of Style (16th Edition):
McMahon, Aoife Christina. “Examination of multiple SynGAP isoforms in mammalian central neurons.” 2011. Doctoral Dissertation, University of Edinburgh. Accessed February 27, 2021.
http://hdl.handle.net/1842/5621.
MLA Handbook (7th Edition):
McMahon, Aoife Christina. “Examination of multiple SynGAP isoforms in mammalian central neurons.” 2011. Web. 27 Feb 2021.
Vancouver:
McMahon AC. Examination of multiple SynGAP isoforms in mammalian central neurons. [Internet] [Doctoral dissertation]. University of Edinburgh; 2011. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/1842/5621.
Council of Science Editors:
McMahon AC. Examination of multiple SynGAP isoforms in mammalian central neurons. [Doctoral Dissertation]. University of Edinburgh; 2011. Available from: http://hdl.handle.net/1842/5621
27.
Alzahrani, Mohammed.
The effect of alternative splicing on key regulators of the integrated stress response.
Degree: 2016, IUPUI
URL: http://hdl.handle.net/1805/11106
► Indiana University-Purdue University Indianapolis (IUPUI)
The protein kinase General control non-derepressible-2 (GCN2) is a key regulator of the Integrated stress response that responds to various…
(more)
▼ Indiana University-Purdue University Indianapolis (IUPUI)
The protein kinase General control non-derepressible-2 (GCN2) is a key regulator of the Integrated stress response that responds to various stress signals, including nutritional deprivation. As a result of high levels of uncharged tRNAs during amino acid depletion, GCN2 phosphorylates serine-51 of the α subunit of eukaryotic initiation factor-2 (eIF2), a translation factor that delivers initiator tRNA to ribosomes. Phosphorylation of eIF2α inhibits general translation, which conserves energy and nutrients and facilitates reprogramming of gene expression for remediation of stress damage. Phosphorylation of eIF2α also directs preferential translation of specific transcription factors, such as ATF4. ATF4 reprograms gene expression to alleviate stress damage; however, under chronic stress, ATF4 directs the transcriptional expression of CHOP, which can trigger apoptosis. Because multiple stresses can induce eIF2α phosphorylation and translational control in mammals, this pathway is referred to as the Integrated stress response.
GCN2 and CHOP are subject to alternative splicing that results in multiple transcripts that differ in the 5'-end of the gene transcripts. However, the effect of the different GCN2 and CHOP isoforms on their function and regulation have not been investigated. Our data suggests that GCN2 is alternatively spliced into five different transcripts and the beta isoform of GCN2 is most abundant. Also alternative splicing of CHOP creates two CHOP transcripts with different 5'-leaders encoding inhibitory upstream open reading frames that are critical for translational control of CHOP during stress. This study suggests that alternative splicing can play an integral role in the implementation and regulation of key factors in the Integrated stress response.
Advisors/Committee Members: Wek, Ronald C., Goebl, Mark G., Mosley, Amber L..
Subjects/Keywords: Alternative splicing; Integrated Stress Response; GCN2; CHOP
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Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Alzahrani, M. (2016). The effect of alternative splicing on key regulators of the integrated stress response. (Thesis). IUPUI. Retrieved from http://hdl.handle.net/1805/11106
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Alzahrani, Mohammed. “The effect of alternative splicing on key regulators of the integrated stress response.” 2016. Thesis, IUPUI. Accessed February 27, 2021.
http://hdl.handle.net/1805/11106.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Alzahrani, Mohammed. “The effect of alternative splicing on key regulators of the integrated stress response.” 2016. Web. 27 Feb 2021.
Vancouver:
Alzahrani M. The effect of alternative splicing on key regulators of the integrated stress response. [Internet] [Thesis]. IUPUI; 2016. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/1805/11106.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Alzahrani M. The effect of alternative splicing on key regulators of the integrated stress response. [Thesis]. IUPUI; 2016. Available from: http://hdl.handle.net/1805/11106
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Iowa State University
28.
Lin, Hung-Ying.
Dissecting complex phenotypes via multiple transcriptome-based GWAS.
Degree: 2018, Iowa State University
URL: https://lib.dr.iastate.edu/etd/17243
► Genome-Wide Association Study (GWAS) have been widely used to detect the QTLs based on Linkage Disequilibrium (LD) relationships between SNPs and QTLs. However, in conventional…
(more)
▼ Genome-Wide Association Study (GWAS) have been widely used to detect the QTLs based on Linkage Disequilibrium (LD) relationships between SNPs and QTLs. However, in conventional GWAS false positive results cause serious concerns. In this research, we developed three different transcriptome-based GWAS approaches which are complementary to conventional SNP-based GWAS. The ability to identify trait-associated genes in these three different methods are supported by cross-validation, transposon knockout mutants, and the analysis of a gene regulatory networks. In summary, we provide novel methods of detecting trait associated loci to further understand the complex gene regulatory systems which will benefit plants, animals, and disease treatment development in the future.
Subjects/Keywords: Alternative Splicing; GWAS; Transcriptome; Bioinformatics; Genetics
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APA ·
Chicago ·
MLA ·
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Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lin, H. (2018). Dissecting complex phenotypes via multiple transcriptome-based GWAS. (Thesis). Iowa State University. Retrieved from https://lib.dr.iastate.edu/etd/17243
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Lin, Hung-Ying. “Dissecting complex phenotypes via multiple transcriptome-based GWAS.” 2018. Thesis, Iowa State University. Accessed February 27, 2021.
https://lib.dr.iastate.edu/etd/17243.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lin, Hung-Ying. “Dissecting complex phenotypes via multiple transcriptome-based GWAS.” 2018. Web. 27 Feb 2021.
Vancouver:
Lin H. Dissecting complex phenotypes via multiple transcriptome-based GWAS. [Internet] [Thesis]. Iowa State University; 2018. [cited 2021 Feb 27].
Available from: https://lib.dr.iastate.edu/etd/17243.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Lin H. Dissecting complex phenotypes via multiple transcriptome-based GWAS. [Thesis]. Iowa State University; 2018. Available from: https://lib.dr.iastate.edu/etd/17243
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Toronto
29.
Tan, June Hui Jun.
A Genome-Scale Analysis of Alternative Splicing Regulation by Splicing Factors in C. elegans.
Degree: PhD, 2018, University of Toronto
URL: http://hdl.handle.net/1807/91985
► Alternative splicing (AS) is a key mechanism that contributes to the high level of complexity present within metazoan proteomes. This process is highly regulated and…
(more)
▼ Alternative splicing (
AS) is a key mechanism that contributes to the high level of complexity present within metazoan proteomes. This process is highly regulated and important for the development for any animal. With advances in high-throughput technologies, our knowledge of the many
AS events that occur in the cell has rapidly increased. However, for many of these events, it is still not known which
splicing factors (SF) are involved, and how they regulate
splicing outcomes. Here, I use a genomic approach in the nematode C. elegans to study how SFs govern
AS events during development. Specifically, for this thesis, I focus on four SFs – ASD-1, FOX-1, EXC-7 and MEC-8. In the first data chapter, I use RNA sequencing, RNA-binding preferences and conservation information to identify likely direct targets of these SFs. I find that
AS regulation by these SFs is often combinatorial and converges upon genes with neuronal and cytoskeletal functions. I further show that loss of these SFs can lead to synergistic defects in the neuromuscular system. Many of these co-regulated
AS events are also developmentally regulated, suggesting a crucial role in development.
In the second data chapter, I then focus on a subset of MEC-8 targets to provide a more detailed view of
splicing regulation. I find that MEC-8 regulates the developmental
AS transitions in multiple transcripts encoding components of the fibrous organelle – a complex crucial for maintaining structural integrity in the worm. Differential mec-8 expression during development likely contributes to the dynamic regulation of these
AS events in a cell- and developmental-stage specific manner. Finally, I find that these
AS patterns can vary among C. elegans natural isolates and differential
splicing is associated with differences in mec-8 expression. These data suggest that the study of natural variation in
AS regulation can provide insight into the regulation of
splicing regulatory pathways.
Advisors/Committee Members: Fraser, Andrew G, Molecular and Medical Genetics.
Subjects/Keywords: Alternative splicing; C. elegans; Genetics; Genomics; 0369
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APA (6th Edition):
Tan, J. H. J. (2018). A Genome-Scale Analysis of Alternative Splicing Regulation by Splicing Factors in C. elegans. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/91985
Chicago Manual of Style (16th Edition):
Tan, June Hui Jun. “A Genome-Scale Analysis of Alternative Splicing Regulation by Splicing Factors in C. elegans.” 2018. Doctoral Dissertation, University of Toronto. Accessed February 27, 2021.
http://hdl.handle.net/1807/91985.
MLA Handbook (7th Edition):
Tan, June Hui Jun. “A Genome-Scale Analysis of Alternative Splicing Regulation by Splicing Factors in C. elegans.” 2018. Web. 27 Feb 2021.
Vancouver:
Tan JHJ. A Genome-Scale Analysis of Alternative Splicing Regulation by Splicing Factors in C. elegans. [Internet] [Doctoral dissertation]. University of Toronto; 2018. [cited 2021 Feb 27].
Available from: http://hdl.handle.net/1807/91985.
Council of Science Editors:
Tan JHJ. A Genome-Scale Analysis of Alternative Splicing Regulation by Splicing Factors in C. elegans. [Doctoral Dissertation]. University of Toronto; 2018. Available from: http://hdl.handle.net/1807/91985
University of Southern California
30.
Zhang, Jing.
Isoform quantification and splicing regulation analysis in
RNA-seq studies.
Degree: PhD, Electrical Engineering, 2015, University of Southern California
URL: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/343497/rec/3668
► The rapid advances in high-throughput sequencing technologies provide us an opportunity to dissect transcriptomes with unprecedented resolution. Based on RNA-seq studies, alternative splicing has become…
(more)
▼ The rapid advances in high-throughput sequencing
technologies provide us an opportunity to dissect transcriptomes
with unprecedented resolution. Based on RNA-seq studies,
alternative splicing has become more and more appreciated
as a key
mechanism in higher eukaryotes to expand transcriptomes by
generating multiple isoforms from a single gene. Therefore,
accurate quantification of transcript isoforms and discovery of
splicing regulation rules are important to understand biological
processes such
as tissue differentiation and cell development,
where
alternative splicing plays an essential role. However,
RNA-seq experiments, which randomly sample the short fragments from
the transcriptome, exhibit distinct data characteristics from
previous techniques and thus await the development of powerful
computational methods. ❧ First and foremost, we present a
weighted-log-likelihood expectation maximization method on isoform
quantification (WemIQ). WemIQ integrates fragment length
information and distributes reads among isoforms through an
expectation maximization (EM) algorithm. More importantly, the
weighted log-likelihood is used to handle both inter- and intra-
gene bias. Simulation and real data analyses show that, compared
with other methods, WemIQ significantly improves the quantification
of isoform expression, exon inclusion ratios, and gene expression
under a variety of gene structures and provides robust mRNA
measurements across different datasets for direct comparisons. ❧
Then, we tried to decipher the
splicing code from the context
aspect through identification of
splicing regulatory elements
(SREs). The fact that a variety of other biological signals
cooperatively govern the
splicing pattern indicates the necessity
of developing novel tools to incorporate information from multiple
sources to improve
splicing factor binding sites prediction. Under
this context, we proposed a Varying Effect Regression for
Splicing
Elements (VERSE) to discover intronic SREs in the proximity of exon
junctions by integrating other biological features. It may serve
as
a powerful tool to not only discover the
splicing elements by
incorporating additional informative signals but also precisely
quantify their varying contribution under different biological
context. ❧ At last, we investigated the structure aspect of
splicing regulation by performing a genomic study of RNA secondary
structures around splice sites in humans, mice, fruit flies, and
nematodes. We observe that GC content around splice sites is
closely associated with the splice site usage in multiple species.
RNA secondary structure is the possible explanation, because the
structural stability difference among
alternative splice sites,
constitutive splice sites, and skipped splice sites can be
explained by the GC content difference.
Alternative splice sites
tend to be GC-enriched and exhibit more stable RNA secondary
structures in all of the considered species. In humans and mice,
splice sites of first exons and long exons tend to be GC-enriched
and hence form more stable…
Advisors/Committee Members: Kuo, C.-C. JayChen, Liang (Committee Chair), Waterman, Michael S. (Committee Member), Sun, Fengzhu Z. (Committee Member), Haldar, Justin P. (Committee Member).
Subjects/Keywords: RNA-seq; alternative splicing; gene expression regulation
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zhang, J. (2015). Isoform quantification and splicing regulation analysis in
RNA-seq studies. (Doctoral Dissertation). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/343497/rec/3668
Chicago Manual of Style (16th Edition):
Zhang, Jing. “Isoform quantification and splicing regulation analysis in
RNA-seq studies.” 2015. Doctoral Dissertation, University of Southern California. Accessed February 27, 2021.
http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/343497/rec/3668.
MLA Handbook (7th Edition):
Zhang, Jing. “Isoform quantification and splicing regulation analysis in
RNA-seq studies.” 2015. Web. 27 Feb 2021.
Vancouver:
Zhang J. Isoform quantification and splicing regulation analysis in
RNA-seq studies. [Internet] [Doctoral dissertation]. University of Southern California; 2015. [cited 2021 Feb 27].
Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/343497/rec/3668.
Council of Science Editors:
Zhang J. Isoform quantification and splicing regulation analysis in
RNA-seq studies. [Doctoral Dissertation]. University of Southern California; 2015. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/343497/rec/3668
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Open Access Theses and Dissertations
