Molecular basis of translation termination at noncanonical stop codons in human mitochondria

• 成果类型: Article
• 署名作者: Saurer, Martin; Leibundgut, Marc; Nadimpalli, Hima Priyanka; Scaiola, Alain; Schonhut, Tanja; Lee, Richard G.; Siira, Stefan J.; Rackham, Oliver; Dreos, Rene; Lenarcic, Tea; Kummer, Eva; Gatfield, David; Filipovska, Aleksandra; Ban, Nenad
• 署名单位: Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Lausanne; Harry Perkins Institute of Medical Research; University of Western Australia; Queen Elizabeth II Medical Centre; University of Western Australia; University of Western Australia; Perth Childrens Hospital; The Kids Research Institute Australia; Curtin University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9690
• DOI: 10.1126/science.adf9890
• 发表日期: 2023-05-05
• 页码: 531-536
• 关键词: genetic-code; EVOLUTION; mtrf1; uaa

摘要

The genetic code that specifies the identity of amino acids incorporated into proteins during protein synthesis is almost universally conserved. Mitochondrial genomes feature deviations from the standard genetic code, including the reassignment of two arginine codons to stop codons. The protein required for translation termination at these noncanonical stop codons to release the newly synthesized polypeptides is not currently known. In this study, we used gene editing and ribosomal profiling in combination with cryo-electron microscopy to establish that mitochondrial release factor 1 (mtRF1) detects noncanonical stop codons in human mitochondria by a previously unknown mechanism of codon recognition. We discovered that binding of mtRF1 to the decoding center of the ribosome stabilizes a highly unusual conformation in the messenger RNA in which the ribosomal RNA participates in specific recognition of the noncanonical stop codons.