Chimeric mitochondrial peptides from contiguous regular and swinger RNA

Abstract

Previous mass spectrometry analyses described human mitochondrial peptides entirely translated from swinger RNAs, RNAs where polymerization systematically exchanged nucleotides. Exchanges follow one among 23 bijective transformation rules, nine symmetric exchanges (X ↔ Y, e.g. A ↔ C) and fourteen asymmetric exchanges (X → Y → Z → X, e.g. A → C → G → A), multiplying by 24 DNA's protein coding potential. Abrupt switches from regular to swinger polymerization produce chimeric RNAs. Here, human mitochondrial proteomic analyses assuming abrupt switches between regular and swinger transcriptions, detect chimeric peptides, encoded by part regular, part swinger RNA. Contiguous regular- and swinger-encoded residues within single peptides are stronger evidence for translation of swinger RNA than previously detected, entirely swinger-encoded peptides: regular parts are positive controls matched with contiguous swinger parts, increasing confidence in results. Chimeric peptides are 200 × rarer than swinger peptides (3/100,000 versus 6/1000). Among 186 peptides with > 8 residues for each regular and swinger parts, regular parts of eleven chimeric peptides correspond to six among the thirteen recognized, mitochondrial protein-coding genes. Chimeric peptides matching partly regular proteins are rarer and less expressed than chimeric peptides matching non-coding sequences, suggesting targeted degradation of misfolded proteins. Present results strengthen hypotheses that the short mitogenome encodes far more proteins than hitherto assumed. Entirely swinger-encoded proteins could exist.

Unbiased Mitoproteome Analyses Confirm Non-canonical RNA, Expanded Codon Translations

“…Overall, results confirm translation of non-canonical RNAs (del- and swinger RNAs), and along expanded codons, in addition to detections of other types of non-canonical peptides, such as peptides translated from contiguous regular and swinger-transformed RNA [36].…”

“…Results confirm previous trypsin-biased analyses that detected non-canonical peptides.Detected non-canonical RNAs associate with tryptic and non-tryptic peptides.Detected non-canonical peptides are overwhelmingly incompatible with translation according to the nuclear genetic code, and specifically match the mitochondrial vertebrate genetic code.Overall, results confirm translation of non-canonical RNAs (del- and swinger RNAs), and along expanded codons, in addition to detections of other types of non-canonical peptides, such as peptides translated from contiguous regular and swinger-transformed RNA [36].Proteomic analyses assuming random cleavage detect non-canonical peptides digested by natural proteolysis, expand proteomic coverage.…”

“…They seem produced by the same RNA polymerase as regular RNA, presumably after the RNA polymerase stabilizes in a hypothetical mode similar to that causing punctual nucleotide misinsertions [32], [33], [34]. This is also indicated by contiguity between regular and swinger sequences in the few detected chimeric RNAs, DNAs and peptides that consist of regular and swinger sequences [35], [36].…”

“…(d) The swinger-transformed human mitogenome has more inverted repeats potentially forming stem-loop hairpins than randomly shuffled sequences [42]. (e) Chimeric DNA/RNA [35] and peptides [36] exist. These nucleotide and peptide sequences consist of at least two contiguous parts, where one part is ‘regular’ (= untransformed), the other is swinger-transformed according to one of the 23 potential bijective transformations of nucleotide sequences [19], [20].…”

Long Noncoding Mitochondrial RNAs (LncmtRNAs) as Targets for Cancer Therapy

“…Along that line, an expanding group of evidences indicate that the mitochondrial genome is not only responsible for the synthesis of the canonical 13 proteins, 22 tRNAs and two ribosomal RNAs (12S and 16S). Novel and expanding evidence suggest that mtDNA compensates for reduced length by using little known phenomena that potentially increase DNA's protein coding repertoire, such as so called swinger polymerization, that consists of systematic exchanges between nucleotides during DNA or RNA polymerization, producing so-called swinger sequences [6,7]. These transformations alter gene and mRNA coding properties.…”