Ribosome Collision Is Critical for Quality Control during No-Go Decay
No-go decay (NGD) is a eukaryotic quality control mechanism that evolved to cope with translational arrests. The process is characterized by an endonucleolytic cleavage near the stall sequence, but the mechanistic details are unclear. Our analysis of cleavage sites indicates that cleavage requires m...
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Veröffentlicht in: | Molecular cell 2017-10, Vol.68 (2), p.361-373.e5 |
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Sprache: | eng |
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Zusammenfassung: | No-go decay (NGD) is a eukaryotic quality control mechanism that evolved to cope with translational arrests. The process is characterized by an endonucleolytic cleavage near the stall sequence, but the mechanistic details are unclear. Our analysis of cleavage sites indicates that cleavage requires multiple ribosomes on the mRNA. We also show that reporters harboring stall sequences near the initiation codon, which cannot accommodate multiple ribosomes, are not subject to NGD. Consistent with our model, we uncover an inverse correlation between ribosome density per mRNA and cleavage efficiency. Furthermore, promoting global ribosome collision in vivo resulted in ubiquitination of ribosomal proteins, suggesting that collision is sensed by the cell to initiate downstream quality control processes. Collectively, our data suggest that NGD and subsequent quality control are triggered by ribosome collision. This model provides insight into the regulation of quality control processes and the manner by which they reduce off-target effects.
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•Multiple ribosomes are required on the mRNA for efficient no-go decay•Ribosome density is negatively correlated with the efficiency of no-go decay•Ubiquitination of RPS3 occurs in response to ribosome collision•Ribosome queuing is important for mRNA quality control
Here Simms et al. reveal that stacked or colliding ribosomes are required to elicit no-go decay. In addition, ubiquitination of RPS3 by HEL2 occurs in response to ribosome collision, which may be a trigger for downstream quality control processes. |
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ISSN: | 1097-2765 1097-4164 |
DOI: | 10.1016/j.molcel.2017.08.019 |