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No‐go decay: a quality control mechanism for RNA in translation

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Abstract Eukaryotic cells have evolved multiple quality control mechanisms that recognize and eliminate defective mRNA during the process of translation. One mechanism, referred to as No‐go decay (NGD), targets mRNAs with elongation stalls for degradation initiated by endonucleolytic cleavage in the vicinity of the stalled ribosome. NGD is promoted by the evolutionarily conserved Dom34 and Hbs1 proteins, which are related to the translation termination factors eRF1 and eRF3, respectively. NGD is likely to occur by Dom34/Hbs1 interacting with the A site in the ribosome leading to release of the peptide or peptidyl‐tRNA. The process of NGD and/or the function of Dom34/Hbs1 appear to be important in several different biological contexts. Copyright © 2010 John Wiley & Sons, Ltd. This article is categorized under: RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Turnover and Surveillance > Regulation of RNA Stability

Working model for no‐go decay. During translation elongation, the ribosome can be paused for a variety of reasons. If the A site is empty during the prolonged elongation stall, it allows the Dom34/Hbs1 complex to bind to the A site of the stalled ribosome leading to peptidyl‐tRNA hydrolysis and release of the peptide, or release of the peptidyl‐tRNA. At this stage, three events could take place: (1) endonucleolytic cleavage of the mRNA in the vicinity of the stalled ribosome, (2) release of the stalled ribosome, and (3) degradation of the nascent peptide or the peptidyl‐tRNA via the ubiquitin (Ub)–proteasome system. Note that mRNA cleavage could possibly occur before the peptidyl‐tRNA hydrolysis or the release of the peptidyl‐tRNA. In any case, the mRNA fragments would be exonucleolytically digested by the exosome and Xrn1. The released ribosome might undergo disassembly and degradation. The released tRNA might be recycled.

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