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Structure paper

TitleMolecular basis of translation termination at noncanonical stop codons in human mitochondria.
Journal, issue, pagesScience, Vol. 380, Issue 6644, Page 531-536, Year 2023
Publish dateMay 5, 2023
AuthorsMartin 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 /
PubMed AbstractThe 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 ...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.
External linksScience / PubMed:37141370
MethodsEM (single particle)
Resolution2.9 - 3.6 Å
Structure data

EMDB-16894, PDB-8oin:
55S mammalian mitochondrial ribosome with mtRF1 and P-site tRNA
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-16895, PDB-8oip:
28S mammalian mitochondrial small ribosomal subunit with mtRF1 and P-site tRNA
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-16896, PDB-8oiq:
39S mammalian mitochondrial large ribosomal subunit with mtRF1 and P-site tRNA
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-16897, PDB-8oir:
55S human mitochondrial ribosome with mtRF1 and P-site tRNA
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-16898, PDB-8ois:
28S human mitochondrial small ribosomal subunit with mtRF1 and P-site tRNA
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-16899, PDB-8oit:
39S human mitochondrial large ribosomal subunit with mtRF1 and P-site tRNA
Method: EM (single particle) / Resolution: 2.9 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-K:
Unknown entry

ChemComp-PHE:
PHENYLALANINE

ChemComp-ZN:
Unknown entry

ChemComp-FES:
FE2/S2 (INORGANIC) CLUSTER

ChemComp-SPM:
SPERMINE

ChemComp-SPD:
SPERMIDINE

ChemComp-FME:
N-FORMYLMETHIONINE

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-GDP:
GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying molecule*YM

ChemComp-HOH:
WATER

ChemComp-FS2:
FE-S-O HYBRID CLUSTER

ChemComp-VAL:
VALINE

ChemComp-MET:
METHIONINE

Source
  • sus scrofa (pig)
  • homo sapiens (human)
KeywordsRIBOSOME / mammalian mitochondrial ribosome / release factor mtRF1 / non-canonical stop codon / human mitochondrial ribosome

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