AutophagyJul 13, 2026

Genome-wide CRISPR screening reveals how TRIM25 helps break down ribosomes through ribophagy

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jul 14, 2026

Abstract

Identifying the ubiquitin ligase TRIM25 reveals its role in ribophagy, a process essential for maintaining ribosome quality.

Ribophagy directs the degradation of nonfunctional ribosomes through a cellular cleanup process.
Impairment of ribophagy may contribute to disorders related to ribosome quality control, known as ribosomopathies.
Genome-wide screening identified TRIM25 as a critical regulator of ribophagy.
TRIM25 binds specifically to ribosomes during ribophagy induction and facilitates their degradation by ubiquitination.
Activation of ribophagy occurs in response to poly(I:C) treatment, which simulates a viral infection, and is dependent on TRIM25.

Simplified

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.

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Genome-wide CRISPR screening reveals how TRIM25 helps break down ribosomes through ribophagy

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