Dissertation/Thesis Abstract

Regulators and effectors of Musashi-dependent translational control
by Cragle, Chad Edward, Ph.D., University of Arkansas for Medical Sciences, 2014, 165; 3621659
Abstract (Summary)

Post-transcriptional regulation of gene expression is critical for a variety of early developmental transitions, cell cycle progression, and control of somatic cell function. A predominant regulatory paradigm is selective control of mRNA translation. Recent advances have demonstrated the diverse array mRNA translational control processes. My focus here is on the RNA-binding protein, Musashi. Previous studies have shown Musashi to be critical during early development and stem cell self-renewal. Further, aberrant Musashi activity is emerging as a potent driver of cancer progression in many malignancies. In Xenopus laevis oocytes, Musashi directs polyadenylation and translational activation of mRNAs required for cell cycle control through previously unknown mechanisms. I identify GLD2, PARN and ePAB as Musashi co-associated proteins. Further, GLD2 and ePAB are demonstrated to be critical for Musashi-directed polyadenylation and translational activation of target mRNAs. An emergent issue in regulated mRNA translation is the number of mRNA 3' UTRs that contain multiple distinct regulatory elements with unique properties necessitating functional integration. Based on our mass spectrometry data comparing co-associated factors interacting with the functionally antagonistic Musashi and CPEB proteins, I propose a potential mechanism of signal integration between distinct regulatory RNA binding proteins through a common shared scaffold complex. These advances constitute the first known mechanisms of Musashi-mediated translational activation and indicate that regulated mRNA translation is likely to be much more complex than originally anticipated.

Indexing (document details)
Advisor: MacNicol, Angus M.
Commitee: Chambers, Timothy, Kelly, Thomas, Sheets, Michael D., Simmen, Frank A.
School: University of Arkansas for Medical Sciences
Department: Interdisciplinary Biomedical Sciences
School Location: United States -- Arkansas
Source: DAI-B 75/09(E), Dissertation Abstracts International
Subjects: Molecular biology, Cellular biology, Developmental biology
Keywords: Musashi, Polyadenylation, Stem cell, Translation, Xenopus, mRNA
Publication Number: 3621659
ISBN: 9781303929328
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