I. mRNA Localization, Translation and Degradation
II. P-bodies and the mRNA Cycle
Part I: mRNA Localization, Translation and Degradation
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The control of mRNA production and function is a key aspect of the regulation of gene expression. In the first part of this lecture, I will discuss how in eukaryotic cells, the control of mRNA localization, translation and degradation in the cytoplasm allow for the proper regulation of the amount, duration, and location of protein production. The basic mechanisms of these processes are understood and reveal that the mechanisms of localization, translation, and degradation are interconnected. The unique properties of each mRNA are dictated by its intrinsic interactions with cellular machines, as well as its complement of mRNA specific RNA binding proteins and miRNAs. Strikingly, mRNPs are dynamic and can be modulated by protein modifications as well as by modification of the mRNA itself, thereby providing a diversity of targets for the regulation of mRNA function in response to extracellular signals.
In the second part of this lecture, I will provide an overview of why the regulation of translation and mRNA degradation is an important aspect of the control of gene expression in eukaryotic cells. In addition to the translating pool of mRNAs associated with polysomes, recent experiments have identified P-bodies and stress granules as specific cytoplasmic compartments wherein untranslated mRNAs accumulate. In addition to mRNAs, P-bodies tend to contain translation repressors and mRNA degradative enzymes, while stress granules reflect mRNAs in association with some translation initiation factors and RNA binding proteins. P-bodies and stress granules interact and suggest a dynamic process wherein eukaryotic mRNAs remodel their interacting proteins and enter and exit translation, thereby affecting the control of mRNAs in the cytoplasm. We are interested in defining the mechanisms by which P-bodies and stress granules assemble and how cells regulate the movement of mRNAs between these different biochemical and cell biological compartments. Several approaches will be described including biochemical and genetic analyses of known proteins modulating these events, as well as the identification of new factors affecting P-body and stress granule formation and function.
Roy Parker a professor of chemistry and biochemistry and Cech-Leinwand Endowed Chair of Biochemistry at the University of Colorado, Boulder and an Investigator of the Howard Hughes Medical Institute. Prior to joining the University of Colorado in 2012, Parker was a Professor of Molecular and Cellular Biology at the University of Arizona.
Dr. Parker received his B.S. in chemistry from Carnegie Mellon University, his Ph.D. in genetics from the University of California, San Francisco and he was a postdoctoral fellow at the University of Massachusetts Medical School.
Parker has a long standing interest in understanding the molecular mechanisms that regulate eukaryotic mRNA stability and translation rate. He has received numerous awards for his work including an NIH Merit Award and election to the National Academy of Sciences.
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- Antony Hyman iBioSeminar: Organization of Cytoplasm
- Ruth Lehmann iBioSeminar: RNA Regulation
- Trudi Schupbach iBioSeminar: Gurken RNA Localization
- Phillip A. Sharp's iBioMagazine: RNA Splicing: What is a Gene?
Buchan JR, Parker R. Eukaryotic stress granules: the ins and outs of translation. Mol Cell. 2009 Dec 25;36(6):932-41.
Balagopal V, Parker R. Polysomes, P bodies and stress granules: states and fates of eukaryotic mRNAs. Curr Opin Cell Biol. 2009 Jun;21(3):403-8.
Franks TM, Lykke-Andersen J. The control of mRNA decapping and P-body formation. Mol Cell. 2008 Dec 5;32(5):605-15.