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.
|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|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be