Hungry Codons Promote Frameshifting in Human Mitochondrial Ribosomes

• Published in: Science (American Association for the Advancement of Science) Vol. 327; no. 5963; p. 301
• Main Authors: Temperley, Richard, Richter, Ricarda, Dennerlein, Sven, Lightowlers, Robert N, Chrzanowska-Lightowlers, Zofia M
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 15.01.2010; The American Association for the Advancement of Science
• Subjects: 3' Untranslated Regions; Amino acids; Arginine - genetics; Biological and medical sciences; Brevia; Cellular biology; Classical genetics, quantitative genetics, hybrids; Codon, Terminator - genetics; Codons; Endoribonucleases - metabolism; Frameshifting, Ribosomal; Fundamental and applied biological sciences. Psychology; Genes, Mitochondrial; Genetics of eukaryotes. Biological and molecular evolution; Human; Humans; Mitochondria; Mitochondria - genetics; Mitochondria - ultrastructure; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Open Reading Frames; Peptide Termination Factors - genetics; Peptide Termination Factors - metabolism; Ribonucleic acid; Ribosomes; Ribosomes - genetics; Ribosomes - metabolism; RNA; RNA - genetics; RNA - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Mitochondrial; Signal transduction; Stop codon; Terminator codon; Three prime untranslated regions; Human; Mitochondria; Mitochondrial DNA; Codon; Ribosome; Phase shift
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1180674

Human mitochondria are not strict adherents to the universal genetic code, with modifications that include the apparent recoding of two arginine triplets to termination signals. This use of both AGA and AGG occurs rarely in other mammals, and this putative change has long posed a challenging conundrum. A -1 mitoribosome frameshift upstream of the rare codons would necessitate recognition of only the conventional UAA and UAG termination codons. By using a sequence-specific endoribonuclease, we show that the rare arginine codons, presumably in association with other cis elements, promote frameshifting in human mitoribosomes.