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Genome-wide CRISPR-Cas9-based screening revealed the role of ubiquitin ligase TRIM25 in ribosome degradation via ribophagy.

Created on 13 Jul 2026

Authors

Julia Golubeva, Alexey Mikhailov, Nikita Shepelev, Elizaveta Pleshko, Ekaterina Guseva, Vera Sidorova, Elena Shagimardanova, Nadezda Andrianova, Egor Plotnikov, Dmitry Karpov, Svetlana Novikova, Victor Zgoda, Maria Rubtsova, Olga Dontsova, Petr Sergiev

Published in

Autophagy. Jul 13, 2026. Epub Jul 13, 2026.

Abstract

Ribophagy is a crucial mechanism that maintains ribosome homeostasis in the cell by directing nonfunctional ribosomes to degradation via macroautophagy/autophagy. Impaired ribophagy may lead to ribosome quality control disorders and may consequently be associated with various diseases known as ribosomopathies. This topic has been actively studied over the past decade, but the complete mechanism of ribophagy is not fully understood. To study the mechanism of ribophagy, we performed a genome-wide CRISPR-Cas9-based screening using a fluorescent ribophagy reporter, which is a cell line with ribosomes carrying RPL29 fused with mCherry and GFP fluorescent proteins. Using the genome-wide Brunello library of guide RNAs, we identified the most promising targets for further study, including the ubiquitin ligase TRIM25, for which we have shown specific binding to the ribosome during ribophagy induction, leading to ubiquitination of the ribosome on the nascent peptide chain and degradation of the whole ribosome. Our findings also demonstrated that poly(I:C) treatment, which mimics viral infection, activates ribophagy in a TRIM25-dependent manner, suggesting the ribophagy pathway could be an antiviral defense mechanism. Taken together, we discovered a novel regulator of ribophagy, TRIM25, which provides new insights into the regulation of selective autophagy in the context of ribosomopathies.

PMID:
42438948
Bibliographic data and abstract were imported from PubMed on 13 Jul 2026.

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