Item – Theses Canada

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OCLC number
1019489511
Link(s) to full text
LAC copy
Author
Saltzman, Arneet L.
Title
Regulation of Core Splicing Factors by Alternative Splicing and Nonsense-mediated mRNA Decay.
Degree
Ph. D. -- University of Toronto, 2011
Publisher
Ottawa : Library and Archives Canada = Bibliothèque et Archives Canada, 2012.
Description
1 online resource
Notes
Includes bibliographical references.
Abstract
<?Pub Inc> The majority of human genes are transcribed into a precursor messenger RNA (pre-mRNA) that is processed to produce multiple mRNA variants through alternative splicing. Although alternative splicing is known for its role in generating proteomic diversity, it can also regulate gene expression by introducing premature termination codons that target the spliced transcript for nonsense-mediated mRNA decay (AS-NMD). In order to understand the impact of AS-NMD on gene expression, I performed quantitative AS microarray profiling of NMD-inhibited human cells. Using this system, I address the prevalence, ' trans'-acting factor requirements and the range of cellular functions regulated by AS-NMD. While this pathway had been implicated in homeostatic feedback regulation of genes encoding splicing-regulatory proteins, my results revealed highly conserved alternative exons regulated by AS-NMD in genes encoding basal or 'core' splicing factors. I further characterized one of these exons in the gene encoding SmB/B', and demonstrated that SmB/B' autoregulates its expression through AS-NMD. Furthermore, AS profiling revealed that knockdown of this core splicing factor affects the inclusion levels of additional alternative exons enriched in genes with functions in RNA processing and RNA binding. In summary, my results reveal a role for AS-NMD in regulating the expression of core splicing factors, as well as a role for the core spliceosomal machinery in coordinating a network of alternative exons in RNA processing factor genes.
ISBN
9780494780121
0494780126