4.8 Article

Distinct elongation stalls during translation are linked with distinct pathways for mRNA degradation

Journal

ELIFE
Volume 11, Issue -, Pages -

Publisher

eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.76038

Keywords

no-go decay; codon-optimality-mediated decay; SYH1; quality control; translation; mRNA decay; S; cerevisiae

Categories

Funding

  1. Canadian Institutes of Health Research Foundation [FDN-159913]
  2. National Institutes of Health [(R37GM059425), 5T32GM135131-02]

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This study investigates the role of Syh1 and Smy2 in coordinating translation repression and mRNA decay in Saccharomyces cerevisiae. The authors demonstrate that the Syh1/Smy2-mediated pathway acts redundantly and compensates for impaired Hel2-dependent NGD. Importantly, the NGD factors identified in this study are not involved in the degradation of mRNAs enriched in non-optimal codons.
Key protein adapters couple translation to mRNA decay on specific classes of problematic mRNAs in eukaryotes. Slow decoding on non-optimal codons leads to codon-optimality-mediated decay (COMD) and prolonged arrest at stall sites leads to no-go decay (NGD). The identities of the decay factors underlying these processes and the mechanisms by which they respond to translational distress remain open areas of investigation. We use carefully designed reporter mRNAs to perform genetic screens and functional assays in Saccharomyces cerevisiae. We characterize the roles of Hel2, Syh1, and Smy2 in coordinating translational repression and mRNA decay on NGD reporter mRNAs, finding that Syh1 and, to a lesser extent its paralog Smy2, act in a distinct pathway from Hel2. This Syh1/Smy2-mediated pathway acts as a redundant, compensatory pathway to elicit NGD when Hel2-dependent NGD is impaired. Importantly, we observe that these NGD factors are not involved in the degradation of mRNAs enriched in non-optimal codons. Further, we establish that a key factor previously implicated in COMD, Not5, contributes modestly to the degradation of an NGD-targeted mRNA. Finally, we use ribosome profiling to reveal distinct ribosomal states associated with each reporter mRNA that readily rationalize the contributions of NGD and COMD factors to degradation of these reporters. Taken together, these results provide new insight into the role of Syh1 and Smy2 in NGD and into the ribosomal states that correlate with the activation of distinct pathways targeting mRNAs for degradation in yeast.

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