ArticleThe EMBO journal2025
Single-protein/RNA imaging reveals ZNF598 as a limiting factor in resolving collided ribosomes.
Article in The EMBO journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- eIF5A and polyamines restrict mRNA levels in response to ribosome stalls.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Role of ZNF598 in Translational Quality Control: Mechanisms and Emerging Biological Functions.Biology · 2026Review
- NNature · 2026Article
- Bridging single-molecule and genome-wide studies of cellular mRNA translation.RNA (New York, N.Y.) · 2026Review
- Ribosome Molecular Aging Shapes Translation Dynamics.bioRxiv : the preprint server for biology · 2026Article
- TFEB coordinates autophagosome biogenesis and ribophagy during starvation via SQSTM1.Science advances · 2026Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Ribosome-associated protein quality control (RQC) is a surveillance system that identifies and processes aberrant mRNAs with collided ribosomes. ZNF598 plays a key role by ubiquitinating the 40S subunit of collided ribosomes. However, how ZNF598 distinguishes stalled from transient ribosome collisions remains unclear. To address this, we developed a method to visualize the binding of a single protein to a specific mRNA while simultaneously determining its translation status. By endogenously tagging ZNF598 with HaloTag, we observed its strong interaction with RQC reporter mRNAs. We discovered that multiple ZNF598s engage with a single RQC mRNA, suggesting that ZNF598 recognizes more than just the leading collided ribosome in a queue. Overexpressing ZNF598 increased the ribosomal clearance rate, indicating that it is a rate-limiting factor for RQC. Interestingly, a subset of supposedly "normal" mRNAs may be damaged and targeted by ZNF598, underscoring the importance of RQC to maintain the proteome quality even in unstressed conditions. Under global UV-induced RNA damage, ZNF598 recruitment to the reporter RQC mRNA diminished, highlighting its role as a limiting factor in managing widespread ribosome collisions.
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Registered trials
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