title: Codon-reading specificities of mitochondrial release factors and translation termination at non-standard stop codons.
abstract: A key feature of mitochondrial translation is the reduced number of transfer RNAs and reassignment of codons. For human mitochondria, a major unresolved problem is how the set of stop codons are decoded by the release factors mtRF1a and mtRF1. Here we present three-dimensional structural models of human mtRF1a and mtRF1 based on their homology to bacterial RF1 in the codon recognition domain, and the strong conservation between mitochondrial and bacterial ribosomal RNA in the decoding region. Sequence changes in the less homologous mtRF1 appear to be correlated with specific features of the mitochondrial rRNA. Extensive computer simulations of the complexes with the ribosomal decoding site show that both mitochondrial factors have similar specificities and that neither reads the putative vertebrate stop codons AGA and AGG. Instead, we present a structural model for a mechanism by which the ICT1 protein causes termination by sensing the presence of these codons in the A-site of stalled ribosomes.
authors.affiliation: 1] Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, Box 596, SE-751 24 Uppsala, Sweden [2].
authors.forename: Christoffer
authors.initials: C
authors.lastname: Lind
authors.affiliation: 1] Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, Box 596, SE-751 24 Uppsala, Sweden [2].
authors.forename: Johan
authors.initials: J
authors.lastname: Sund
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, Box 596, SE-751 24 Uppsala, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Aqvist
mesh_terms: D000595:Amino Acid Sequence; D018388:Codon, Terminator; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009154:Mutation; D010454:Peptide Termination Factors / Q000737:chemistry*; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012335:RNA, Ribosomal / Q000737:chemistry; D012343:RNA, Transfer / Q000378:metabolism*; D012270:Ribosomes / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D013824:Thermus / Q000378:metabolism; D061806:Transcription Termination, Genetic
chemical_list: D018388:Codon, Terminator; C523958:MTRF1L protein, human; D024101:Mitochondrial Proteins; D010454:Peptide Termination Factors; D012335:RNA, Ribosomal; C070289:peptide chain release factor, mammalian; D012343:RNA, Transfer