Abstract
Frameshifting protein translation occasionally results from insertion of amino acids at isolated mono- or dinucleotide-expanded codons by tRNAs with expanded anticodons. Previous analyses of two different types of human mitochondrial MS proteomic data (Fisher and Waters technologies) detect peptides entirely corresponding to expanded codon translation. Here, these proteomic data are reanalyzed searching for peptides consisting of at least eight consecutive amino acids translated according to regular tricodons, and at least eight adjacent consecutive amino acids translated according to expanded codons. Both datasets include chimerically translated peptides (mono- and dinucleotide expansions, 42 and 37, respectively). The regular tricodon-encoded part of some chimeric peptides corresponds to standard human mitochondrial proteins (mono- and dinucleotide expansions, six (AT6, CytB, ND1, 2xND2, ND5) and one (ND1), respectively). Chimeric translation probably increases the diversity of mitogenome-encoded proteins, putatively producing functional proteins. These might result from translation by tRNAs with expanded anticodons, or from regular tricodon translation of RNAs where transcription/posttranscriptional edition systematically deleted mono- or dinucleotides after each trinucleotide. The pairwise matched combination of adjacent peptide parts translated from regular and expanded codons strengthens the hypothesis that translation of stretches of consecutive expanded codons occurs. Results indicate statistical translation producing distributions of alternative proteins. Genetic engineering should account for potential unexpected, unwanted secondary products.
Highlights
The low stability of codon-anticodon duplexes does not enable mRNA translation without a ribosome stabilizing this interaction long enough to enable peptide elongation [1]
In addition to tetracoding sequences predicted by alignment methods, peptides corresponding in their entireties to the translation of tetra- and pentacodons have been detected in MS data (produced by the medium accuracy Thermo Fisher (Illkirch, France), and the high accuracy Waters (Milford, MA, USA) technologies) from the human mitochondrial peptidome [62,63,64,65,66,67]
Natural stop suppression in mitogenes can be predicted based on alignment analyses [52,84,85,86,87,88,89,90,91], and observed distributions of amino acids inserted at stops [62,63,64,65,66,67] match genetic code evolution [92,93,94,95] and coding symmetries in the genetic code [96]
Summary
The low stability of codon-anticodon duplexes does not enable mRNA translation without a ribosome stabilizing this interaction long enough to enable peptide elongation [1]. Ribosomes are very complex molecules [2,3,4] resulting from complex accretion histories [5,6,7,8,9], meaning that tRNA and tRNA-like structures accreted serially, becoming over time modern rRNA. Some kind of translation presumably occurred before ribosomes evolved, possibly including direct codon-amino acid interactions [24,25,26,27,28,29,30,31]
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