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4EHP and GIGYF1/2 mediate translation-coupled messenger RNA decay

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Item Type:Article
Title:4EHP and GIGYF1/2 mediate translation-coupled messenger RNA decay
Creators Name:Weber, R. and Chung, M.Y. and Keskeny, C. and Zinnall, U. and Landthaler, M. and Valkov, E. and Izaurralde, E. and Igreja, C.
Abstract:Current models of mRNA turnover indicate that cytoplasmic degradation is coupled with translation. However, our understanding of the molecular events that coordinate ribosome transit with the mRNA decay machinery is still limited. Here, we show that 4EHP-GIGYF1/2 complexes trigger co-translational mRNA decay. Human cells lacking these proteins accumulate mRNAs with prominent ribosome pausing. They include, among others, transcripts encoding secretory and membrane-bound proteins or tubulin subunits. In addition, 4EHP-GIGYF1/2 complexes fail to reduce mRNA levels in the absence of ribosome stalling or upon disruption of their interaction with the cap structure, DDX6, and ZNF598. We further find that co-translational binding of GIGYF1/2 to the mRNA marks transcripts with perturbed elongation to decay. Our studies reveal how a repressor complex linked to neurological disorders minimizes the protein output of a subset of mRNAs.
Keywords:mRNA Decay, Translation, Ribosome Pausing, DDX6, GYF Domain, Endoplasmic Reticulum, Signal Peptide, Nascent Chain, Tubulin
Source:Cell Reports
Publisher:Cell Press / Elsevier
Page Range:108262
Date:13 October 2020
Official Publication:https://doi.org/10.1016/j.celrep.2020.108262
PubMed:View item in PubMed

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