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Review
. 2021 Apr 1;81(7):1372-1383.
doi: 10.1016/j.molcel.2021.02.022. Epub 2021 Mar 12.

Ribosome states signal RNA quality control

Affiliations
Review

Ribosome states signal RNA quality control

Karole N D'Orazio et al. Mol Cell. .

Abstract

Eukaryotic cells integrate multiple quality control (QC) responses during protein synthesis in the cytoplasm. These QC responses are signaled by slow or stalled elongating ribosomes. Depending on the nature of the delay, the signal may lead to translational repression, messenger RNA decay, ribosome rescue, and/or nascent protein degradation. Here, we discuss how the structure and composition of an elongating ribosome in a troubled state determine the downstream quality control pathway(s) that ensue. We highlight the intersecting pathways involved in RNA decay and the crosstalk that occurs between RNA decay and ribosome rescue.

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Conflict of interest statement

Declaration of interests R.G. is a member of the scientific advisory board at the journal Molecular Cell.

Figures

Figure 1:
Figure 1:
Model for mRNA decay on nonoptimal mRNA. The N-terminus of Not5 recognizes an empty E site on a slowly elongating ribosome. By recruiting CCR4-NOT, Not5 signals canonical Xrn1-mediated mRNA decay.
Figure 2:
Figure 2:
Model for QC on internal ORF-stalled ribosomes. Ribosome collisions signal Hel2-dependent ubiquitination, Syh1-mediated mRNA decay through Xrn1, and both ribosome rescue by RQT (A) and endonucleolytic cleavage by Cue2 followed by Dom34:Hbs1 ribosome rescue (B).
Figure 3:
Figure 3:
Model for QC on poly-A stalled ribosomes. Ribosome stalling on poly-A sequences recruits the SKI complex through an unknown mechanism. The SKI complex then “pulls” on the mRNA from the ribosome and funnels it into the exosome. Figures created with BioRender.com

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