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Ada Doisy Lectures in Biochemistry: Dr. Roy Parker (University of Colorado Boulder), "The Cytoplasmic Life of mRNA"

Event Type
academic, biochemistry
Dr. Emad Tajkhorshid
Medical Sciences Building Auditorium, 506 S. Mathews Avenue, Urbana
Dec 7, 2018   12:00 pm  
Dr. Roy Parker
Sherry Unkraut
Originating Calendar
Biochemistry Department Seminars

The control of mRNA translation, degradation, and localization are critical aspects of theregulation of eukaryotic gene expression. Degradation of mRNAs occurs through a general pathway of deadenylation, which leads to either 3’ to 5’ degradation, or decapping and 5’ to 3’ exonucleolytic decay. All RNAs in cells are also subject to quality control mechanisms that degrade dysfunctional RNAs, which for mRNAs can be due to defects in translation elongation and/or termination. In addition, the decay rates, and quality control, of many non-coding RNAs occurs through a competition of 3’ end additions, and their removal by both stabilizing (such as PARN, TOE1, and USB1) and degrading exonucleases (such as EXOSC10, DIS3L, and DSI3L2). Mutations that disrupt the balance of 3’ end modification and trimming can lead to human diseases such as dyskeratosis congenita. When mRNAs exit translation, they can localize to Pbodies or stress granules, which are cytoplasmic RNP granules. Stress granules are of particular interest since they play roles in the stress response, are similar to neuronal and maternal RNP granules involved in synaptic plasticity and mRNA regulation in early development, respectively, and when mutated can contribute to some degenerative diseases, such as ALS. Stress granules have a complex proteome, a transcriptome dominated by long mRNAs, and appear to form through a combination of protein-protein and intermolecular RNA-RNA interactions. The mechanisms of stress granule formation suggest that the formation of dense networks of interacting RNAs is the lowest energy state for RNA in eukaryotic cells and cells use active mechanisms to prevent pervasive RNA aggregation, revealing novel sites for biological regulation.

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