RQC2 is a major player in peptide release from stalled ribosomes

IF 4.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Structure Pub Date : 2025-04-04 DOI:10.1016/j.str.2025.03.008

Céline Fabret, Emmanuel Giudice, Sophie Chat, Reynald Gillet, Olivier Namy

引用次数: 0

Abstract

Eukaryotic cells prevent the accumulation of potentially toxic aberrant polypeptides and maintain ribosome availability through surveillance and clearance mechanisms, including the evolutionarily conserved ribosome-associated quality control complex (RQC). RQC pathways have been widely investigated, with the identification of several factors ANKZF1/Vms1p, Ptrh1, and Arb1p involved in release/cleavage of the peptide-tRNA from 60S subunits. We aimed here to identify the genes involved in peptide release from stalled ribosomes. Using a genetic screen, we identified a mutant allele of RQC2 as involved in this process. We present the cryoelectron microscopy (cryo-EM) structure of RQC, which reveals how the F340I mutation affects mutant binding. This altered binding, in turn, disrupts the A-site’s ability to bind the tRNA in the presence of Ltn1. These data account for the limitation of C-terminal alanine and threonine (CAT) tailing by the F340I mutation and suggest a model explaining the role of the Rqc2 protein in peptide release.

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来源期刊

Structure 生物-生化与分子生物学

CiteScore

8.90

自引率

1.80%

发文量

155

审稿时长

3-8 weeks

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