ArticleNature chemical biology2024
The eRF1 degrader SRI-41315 acts as a molecular glue at the ribosomal decoding center.
Article in Nature chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Halting translation by the letter with sequence-selective small molecules.Nature chemical biology · 2026Review
- Substrate Binding Relieves Autoinhibition of the Mammalian GCN2 Kinase.bioRxiv : the preprint server for biology · 2026Article
- Ribosome dynamics at the conserved PGP motif governs 2A peptide-bond-skipping efficiency.Nucleic acids research · 2026Article
- Article
- Integrated phenotypic screening and chemical proteomics identifies ETF1 ligands that modulate viral translation and replication.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- MGTbind: a comprehensive database of molecular glue ternary interactome.Nucleic acids research · 2026Article
- Exploring Novel E3 Ligases and Neosubstrates for Molecular Glue Degraders and Therapeutic Applications in Cancer.Oncology research · 2026Review
- Review
- Identification of translation events that drive nonsense-mediated mRNA decay reveals functional roles for noncoding RNAs.bioRxiv : the preprint server for biology · 2025Article
- Review
- Ubiquitin-dependent translation control mechanisms: Degradation and beyond.Cell reports · 2024Review
- The ABCF ATPase New1 resolves translation termination defects associated with specific tRNAArg and tRNALys isoacceptors in the P site.Nucleic acids research · 2024Article
- Therapeutic Nonsense Suppression Modalities: From Small Molecules to Nucleic Acid-Based Approaches.Biomedicines · 2024Review
- The ABCF ATPase New1 resolves translation termination defects associated with specific tRNAbioRxiv : the preprint server for biology · 2024Article
- Enhancing the Small-Scale Screenable Biological Space beyond Known Chemogenomics Libraries with Gray Chemical Matter─Compounds with Novel Mechanisms from High-Throughput Screening Profiles.ACS chemical biology · 2024Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Translation termination is an essential cellular process, which is also of therapeutic interest for diseases that manifest from premature stop codons. In eukaryotes, translation termination requires eRF1, which recognizes stop codons, catalyzes the release of nascent proteins from ribosomes and facilitates ribosome recycling. The small molecule SRI-41315 triggers eRF1 degradation and enhances translational readthrough of premature stop codons. However, the mechanism of action of SRI-41315 on eRF1 and translation is not known. Here we report cryo-EM structures showing that SRI-41315 acts as a metal-dependent molecular glue between the N domain of eRF1 responsible for stop codon recognition and the ribosomal subunit interface near the decoding center. Retention of eRF1 on ribosomes by SRI-41315 leads to ribosome collisions, eRF1 ubiquitylation and a higher frequency of translation termination at near-cognate stop codons. Our findings reveal a new mechanism of release factor inhibition and additional implications for pharmacologically targeting eRF1.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.