Molecular basis of translation termination at noncanonical stop codons in human mitochondria
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Molecular basis of translation termination at noncanonical stop codons in human mitochondria. / Saurer, Martin; Leibundgut, Marc; Nadimpalli, Hima Priyanka; Scaiola, Alain; Schönhut, Tanja; Lee, Richard G; Siira, Stefan J; Rackham, Oliver; Dreos, René; Lenarčič, Tea; Kummer, Eva; Gatfield, David; Filipovska, Aleksandra; Ban, Nenad.
In: Science, Vol. 380, No. 6644, 2023, p. 531-536.Research output: Contribution to journal › Journal article › Research › peer-review
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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
Y1 - 2023
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.
KW - Humans
KW - Codon, Terminator
KW - Cryoelectron Microscopy
KW - Peptide Termination Factors/chemistry
KW - Protein Biosynthesis
KW - Proteins/genetics
KW - Mitochondria/genetics
KW - Peptide Chain Termination, Translational
U2 - 10.1126/science.adf9890
DO - 10.1126/science.adf9890
M3 - Journal article
C2 - 37141370
VL - 380
SP - 531
EP - 536
JO - Science
JF - Science
SN - 0036-8075
IS - 6644
ER -
ID: 346587943