Seligmann Hervé
Unité de Recherche sur les Maladies Infectieuses et Tropicales Émergentes, Faculté de Médecine, URMITE CNRS-IRD 198 UMER 6236, Université de la Méditerranée, Marseille, France.
Comput Struct Biotechnol J. 2016 Jun 29;14:283-97. doi: 10.1016/j.csbj.2016.06.005. eCollection 2016.
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.
先前的质谱分析描述了完全由摆动RNA翻译而来的人类线粒体肽段，摆动RNA是指聚合过程中系统地交换核苷酸的RNA。交换遵循23种双射变换规则中的一种，9种对称交换（X↔Y，例如A↔C）和14种不对称交换（X→Y→Z→X，例如A→C→G→A），使DNA的蛋白质编码潜力增加了24倍。从常规聚合到摆动聚合的突然转变会产生嵌合RNA。在此，假设常规转录和摆动转录之间存在突然转变的人类线粒体蛋白质组学分析检测到了嵌合肽段，其由部分常规、部分摆动的RNA编码。单个肽段内连续的常规编码和摆动编码残基比先前检测到的完全由摆动编码的肽段更能证明摆动RNA的翻译：常规部分是与连续摆动部分相匹配的阳性对照，增加了对结果的信心。嵌合肽段比摆动肽段稀少200倍（3/100,000对6/1000）。在每个常规和摆动部分都有超过8个残基的186个肽段中，11个嵌合肽段的常规部分对应于13个已识别的线粒体蛋白质编码基因中的6个。与部分常规蛋白质匹配的嵌合肽段比与非编码序列匹配的嵌合肽段更稀少且表达量更低，这表明错误折叠的蛋白质会被靶向降解。目前的结果强化了这样的假设，即短的线粒体基因组编码的蛋白质比迄今所认为的要多得多。可能存在完全由摆动编码的蛋白质。
