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

Martin Saurer | Zendy; Marc Leibundgut | Zendy; Hima Priyanka Nadimpalli | Zendy; Alain Scaiola | Zendy; Tanja Schönhut | Zendy; Richard G. Lee | Zendy; Stefan J. Siira | Zendy; Oliver Rackham | Zendy; René Dreos | Zendy; Tea Lenarčič | Zendy; Eva Kummer | Zendy; David Gatfield | Zendy; Aleksandra Filipovska | Zendy; Nenad Ban | Zendy

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

Author(s) -

Martin Saurer,

Marc Leibundgut,

Hima Priyanka Nadimpalli,

Alain Scaiola,

Tanja Schönhut,

Richard G. Lee,

Stefan J. Siira,

Oliver Rackham,

René Dreos,

Tea Lenarčič,

Eva Kummer,

David Gatfield,

Aleksandra Filipovska,

Nenad Ban

Publication year - 2023

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.adf9890

Subject(s) - genetic code , ribosome , stop codon , ribosome profiling , biology , genetics , gene , translation (biology) , reading frame , mitochondrial ribosome , mitochondrial dna , computational biology , messenger rna , rna , open reading frame , peptide sequence

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.

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