TY - JOUR
T1 - Molecular basis of translation termination at noncanonical stop codons in human mitochondria
AU - Saurer, Martin
AU - Leibundgut, Marc
AU - Nadimpalli, Hima Priyanka
AU - Scaiola, Alain
AU - Schönhut, Tanja
AU - Lee, Richard G
AU - Siira, Stefan J
AU - Rackham, Oliver
AU - Dreos, René
AU - Lenarčič, Tea
AU - Kummer, Eva
AU - Gatfield, David
AU - Filipovska, Aleksandra
AU - Ban, Nenad
PY - 2023/5/5
Y1 - 2023/5/5
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85159549112
U2 - 10.1126/science.adf9890
DO - 10.1126/science.adf9890
M3 - Article
C2 - 37141370
SN - 0036-8075
VL - 380
SP - 531
EP - 536
JO - Science (New York, N.Y.)
JF - Science (New York, N.Y.)
IS - 6644
ER -