Natural pyrrolysine-biased translation of stop codons in mitochondrial peptides entirely coded by expanded codons. (October 2020)

• Record Type: Journal Article
• Authors: Seligmann, Hervé; Warthi, Ganesh
• Is Part Of: Bio systems. Volume 196(2020)
• Publication Date: 2020-10
• Subjects: DelRNAs -- RNA editing -- tRNA hopping -- Antitermination -- Stop suppression -- Aminoacylation; Biological systems -- Periodicals; Biology -- Periodicals; Biology -- Periodicals; Evolution -- Periodicals; Biologie -- Périodiques; Évolution -- Périodiques; 570
• DOI: 10.1016/j.biosystems.2020.104180
• Languages: English
• ISSNs: 0303-2647

Abstract

Abstract: During the noncanonical deletion transcription, k nucleotides are systematically skipped/deleted after each transcribed trinucleotide producing deletion-RNAs (delRNAs). Peptides matching delRNAs either result from (a) canonical translation of delRNAs; or (b) noncanonical translation of regular transcripts along expanded codons. Only along frame "0" (start site) (a) and (b) produce identical peptides. Here, mitochondrial mass spectrometry data analyses assume expanded codon/del-transcription with 3 + k (k from 0 to 12) nucleotides. Detected peptides map preferentially on previously identified delRNAs. More peptides were detected for k (1–12) when del-transcriptional and expanded codon translations start sites coincide (i.e. the 0 th frame) than for frames +1 or +2. Hence, both (a) and (b) produced peptides identified here. Biases for frame 0 decrease for k > 2, reflecting codon/anticodon expansion limits. Further analyses find preferential pyrrolysine insertion at stop codons, suggesting Pyl-specific mitochondrial suppressor tRNAs loaded by Pyl-specific tRNA synthetases with unknown origins. Pyl biases at stops are stronger for regular than expanded codons suggesting that Pyl-tRNAs are less competitive with near-cognate tRNAs in expanded codon contexts. Statistical biases for these findings exclude that detected peptides are experimental and/or bioinformatic artefacts implying both del-transcription and expanded codons translation occur in human mitochondria.