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

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

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 journalJournal articleResearchpeer-review

Harvard

Saurer, M, Leibundgut, M, Nadimpalli, HP, Scaiola, A, Schönhut, T, Lee, RG, Siira, SJ, Rackham, O, Dreos, R, Lenarčič, T, Kummer, E, Gatfield, D, Filipovska, A & Ban, N 2023, 'Molecular basis of translation termination at noncanonical stop codons in human mitochondria', Science, vol. 380, no. 6644, pp. 531-536. https://doi.org/10.1126/science.adf9890

APA

Saurer, M., Leibundgut, M., Nadimpalli, H. P., Scaiola, A., Schönhut, T., Lee, R. G., Siira, S. J., Rackham, O., Dreos, R., Lenarčič, T., Kummer, E., Gatfield, D., Filipovska, A., & Ban, N. (2023). Molecular basis of translation termination at noncanonical stop codons in human mitochondria. Science, 380(6644), 531-536. https://doi.org/10.1126/science.adf9890

Vancouver

Saurer M, Leibundgut M, Nadimpalli HP, Scaiola A, Schönhut T, Lee RG et al. Molecular basis of translation termination at noncanonical stop codons in human mitochondria. Science. 2023;380(6644):531-536. https://doi.org/10.1126/science.adf9890

Author

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. / Molecular basis of translation termination at noncanonical stop codons in human mitochondria. In: Science. 2023 ; Vol. 380, No. 6644. pp. 531-536.

Bibtex

@article{b540d35180c340e1866f22395520cb1f,
title = "Molecular basis of translation termination at noncanonical stop codons in human mitochondria",
abstract = "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.",
keywords = "Humans, Codon, Terminator, Cryoelectron Microscopy, Peptide Termination Factors/chemistry, Protein Biosynthesis, Proteins/genetics, Mitochondria/genetics, Peptide Chain Termination, Translational",
author = "Martin Saurer and Marc Leibundgut and Nadimpalli, {Hima Priyanka} and Alain Scaiola and Tanja Sch{\"o}nhut and Lee, {Richard G} and Siira, {Stefan J} and Oliver Rackham and Ren{\'e} Dreos and Tea Lenar{\v c}i{\v c} and Eva Kummer and David Gatfield and Aleksandra Filipovska and Nenad Ban",
year = "2023",
doi = "10.1126/science.adf9890",
language = "English",
volume = "380",
pages = "531--536",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6644",

}

RIS

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