Seligmann Hervé, Warthi Ganesh
The National Natural History Collections, The Hebrew University of Jerusalem, 91404 Jerusalem, Israel.
Aix-Marseille University, IRD, VITROME, Institut Hospitalo-Universitaire Méditerranée-Infection, Marseille, France.
Comput Struct Biotechnol J. 2019 Aug 23;17:1195-1202. doi: 10.1016/j.csbj.2019.08.006. eCollection 2019.
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.
移码蛋白翻译偶尔会因具有扩展反密码子的tRNA在孤立的单核苷酸或二核苷酸扩展密码子处插入氨基酸而产生。先前对两种不同类型的人类线粒体质谱蛋白质组学数据（费舍尔和沃特斯技术）的分析检测到了与扩展密码子翻译完全对应的肽段。在此，对这些蛋白质组学数据进行重新分析，以寻找由至少八个根据常规三联密码子翻译的连续氨基酸以及至少八个根据扩展密码子翻译的相邻连续氨基酸组成的肽段。两个数据集都包含嵌合翻译的肽段（单核苷酸和二核苷酸扩展，分别为42个和37个）。一些嵌合肽段中由常规三联密码子编码的部分对应于标准的人类线粒体蛋白（单核苷酸和二核苷酸扩展，分别为六个（AT6、细胞色素B、ND1、2×ND2、ND5）和一个（ND1））。嵌合翻译可能会增加线粒体基因组编码蛋白的多样性，推测会产生功能性蛋白。这些可能源于具有扩展反密码子的tRNA的翻译，或者源于RNA的常规三联密码子翻译，其中转录/转录后编辑在每个三核苷酸之后系统地删除了单核苷酸或二核苷酸。从常规密码子和扩展密码子翻译的相邻肽段部分的成对匹配组合强化了连续扩展密码子片段发生翻译的假设。结果表明统计翻译产生了替代蛋白的分布。基因工程应考虑潜在的意外、不需要的副产物。
