Avoidance of antisense, antiterminator tRNA anticodons in vertebrate mitochondria.
Protein synthesis (translation) stops at stop codons, codons not complemented by tRNA anticodons. tRNAs matching stops, antitermination (Ter) tRNAs, prevent translational termination, producing dysfunctional proteins. Genomes avoid tRNAs with anticodons whose complement (the anticodon of the 'antisense' tRNA) matches stops. This suggests that antisense tRNAs, which also form cloverleaves, are occasionally expressed. Mitochondrial antisense tRNA expression is plausible, because both DNA strands are transcribed as single RNAs, and tRNA structures signal RNA maturation. Results describe potential antisense Ter tRNAs in mammalian mitochondrial genomes detected by tRNAscan-SE, and evidence for adaptations preventing translational antitermination: genomes possessing Ter tRNAs use less corresponding stop codons; antisense Ter tRNAs form weaker cloverleaves than homologuous non-Ter antisense tRNAs; and genomic stop codon usages decrease with stabilities of codon-anticodon interactions and of Ter tRNA cloverleaves. This suggests that antisense tRNAs frequently function in translation. Results suggest that opposite strand coding is exceptional in modern genes, yet might be frequent for mitochondrial tRNAs. This adds antisense tRNA templating to other mitochondrial tRNA functions: sense tRNA templating, formation and regulation of secondary (light strand DNA) replication origins. Antitermination probably affects mitochondrial degenerative diseases and ageing: pathogenic mutations are twice as frequent in tRNAs with antisense Ter anticodons than in other tRNAs, and species lacking mitochondrial antisense Ter tRNAs have longer mean maximal lifespans than those possessing antisense Ter tRNAs.
Seligmann
Hervé
H
Department of Biology, University of Oslo, Blindern, 3016 Oslo, Norway. herves@bio.uio.no
D000818:Animals; D000926:Anticodon / Q000235:genetics*; D001483:Base Sequence; D018388:Codon, Terminator / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D012313:RNA / Q000235:genetics*; D016372:RNA, Antisense / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012343:RNA, Transfer / Q000235:genetics*; D013045:Species Specificity; D014714:Vertebrates / Q000235:genetics*
D000926:Anticodon; D018388:Codon, Terminator; D016372:RNA, Antisense; D000077278:RNA, Mitochondrial; D012313:RNA; D012343:RNA, Transfer