Science.: co-auth.: group Gatflield

Science. 2023 May 5;380(6644):531-536. doi: 10.1126/science.adf9890. Epub 2023 May 4.

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

Martin Saurer 1Marc Leibundgut 1Hima Priyanka Nadimpalli 2Alain Scaiola 1Tanja Schönhut 1Richard G Lee 3 4 5Stefan J Siira 3 4Oliver Rackham 3 4 5 6René Dreos 2Tea Lenarčič 1Eva Kummer 7David Gatfield 2Aleksandra Filipovska 3 4 5Nenad Ban 1Affiliations expand


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.