TY - JOUR
T1 - The endonuclease cue2 cleaves mRNAs at stalled ribosomes during no go decay
AU - D’Orazio, Karole N.
AU - Wu, Colin Chih Chien
AU - Sinha, Niladri
AU - Loll-Krippleber, Raphael
AU - Brown, Grant W.
AU - Green, Rachel
N1 - Publisher Copyright:
© D’Orazio et al.
PY - 2019/6
Y1 - 2019/6
N2 - Translation of problematic sequences in mRNAs leads to ribosome collisions that trigger a series of quality control events including ribosome rescue, degradation of the stalled nascent polypeptide, and targeting of the mRNA for decay (No Go Decay or NGD). Using a reverse genetic screen in yeast, we identify Cue2 as the conserved endonuclease that is recruited to stalled ribosomes to promote NGD. Ribosome profiling and biochemistry provide strong evidence that Cue2 cleaves mRNA within the A site of the colliding ribosome. We demonstrate that NGD primarily proceeds via Xrn1-mediated exonucleolytic decay and Cue2-mediated endonucleolytic decay normally constitutes a secondary decay pathway. Finally, we show that the Cue2-dependent pathway becomes a major contributor to NGD in cells depleted of factors required for the resolution of stalled ribosome complexes. Together these results provide insights into how multiple decay processes converge to process problematic mRNAs in eukaryotic cells.
AB - Translation of problematic sequences in mRNAs leads to ribosome collisions that trigger a series of quality control events including ribosome rescue, degradation of the stalled nascent polypeptide, and targeting of the mRNA for decay (No Go Decay or NGD). Using a reverse genetic screen in yeast, we identify Cue2 as the conserved endonuclease that is recruited to stalled ribosomes to promote NGD. Ribosome profiling and biochemistry provide strong evidence that Cue2 cleaves mRNA within the A site of the colliding ribosome. We demonstrate that NGD primarily proceeds via Xrn1-mediated exonucleolytic decay and Cue2-mediated endonucleolytic decay normally constitutes a secondary decay pathway. Finally, we show that the Cue2-dependent pathway becomes a major contributor to NGD in cells depleted of factors required for the resolution of stalled ribosome complexes. Together these results provide insights into how multiple decay processes converge to process problematic mRNAs in eukaryotic cells.
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U2 - 10.7554/eLife.49117.001
DO - 10.7554/eLife.49117.001
M3 - Article
C2 - 31219035
AN - SCOPUS:85071845579
SN - 2050-084X
VL - 8
JO - eLife
JF - eLife
M1 - e49117
ER -