Pocketknife tRNA hypothesis: Anticodons in mammal mitochondrial tRNA side-arm loops translate proteins?

Abstract

Peptide elongation proceeds by tRNA anticodons recognizing mRNA codons coding for the tRNA's cognate amino acid. Putatively, tRNAs possess three anticodons because tRNA side and anticodon-arms form similar stem-loop structures. Two lines of evidence indicate that mammal mitochondrial tRNA sidearms function as anticodons: numbers of TΨC-arm ‘anticodons’ matching specific cognates coevolve with that cognate's usage in mitochondrial genomes; and predicted ‘tetragene’ numbers, genes coded by quadruplet codons (tetracodons), coevolve with numbers of expanded anticodons in D-arms, as previously observed between tetragenes and antisense tRNA expanded anticodons. Sidearms with long stems and high GC contents contribute most to tRNA sidearm-tetragene coevolution. Results are compatible with two hypothetical mechanisms for translation by side-arms: crossovers exchange anticodon- and side-arms; tRNA sidearms are excised, aminoacylated and function as isolated stem-loop hairpins (more probable for long, respectively stable branches). Isolated sidearms would resemble recently described armless ‘minimal’ tRNAs. Isolated hairpins might most parsimoniously explain observed patterns. tRNA genes templating for three, rather than one functional tRNA, compress minimal genome size. Results suggest fused tRNA halves form(ed) modern tRNAs, isolated tRNA subparts occasionally translate proteins. Results confirm translational activity by antisense tRNAs, whose anticodons also coevolve with codon usages. Accounting for antisense anticodons improves results for sidearm anticodons.