Complete chemical structures of human mitochondrial tRNAs
Complete chemical structures of human mitochondrial tRNAs
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DOI：
10.1038/s41467-020-18068-6
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发表时间：
2020-08-28
影响因子：
16.6
通讯作者：
Suzuki, Tsutomu
中科院分区：
文献类型：
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作者：
Suzuki, Takeo;Yashiro, Yuka;Suzuki, Tsutomu
线粒体通过氧化磷酸化产生大部分细胞能量。22种线粒体（mt-）tRNA编码的mtDNA翻译呼吸链复合物的基本亚基。mt-tRNA含有由核编码的tRNA修饰酶引入的转录后修饰。它们是准确破译遗传密码以及稳定tRNA所必需的。tRNA修饰的丧失经常导致严重的病理后果。在这里，我们进行了全面的分析所有人类mt-tRNAs的转录后修饰，包括14个以前未知的物种。在22种人类mt-tRNAs中，我们总共发现了18种RNA修饰，在137个位点上（占1575个碱基的8.7%）。提供了负责mt-tRNA修饰的34个基因的最新列表。我们确定了两个基因所需的肌苷（Q）形成的mt-tRNA。我们的研究结果提供了深入了解解码系统的分子机制，并可能有助于阐明异常tRNA修饰引起的人类线粒体疾病的分子发病机制。
Mitochondria generate most cellular energy via oxidative phosphorylation. Twenty-two species of mitochondrial (mt-)tRNAs encoded in mtDNA translate essential subunits of the respiratory chain complexes. mt-tRNAs contain post-transcriptional modifications introduced by nuclear-encoded tRNA-modifying enzymes. They are required for deciphering genetic code accurately, as well as stabilizing tRNA. Loss of tRNA modifications frequently results in severe pathological consequences. Here, we perform a comprehensive analysis of post-transcriptional modifications of all human mt-tRNAs, including 14 previously-uncharacterized species. In total, we find 18 kinds of RNA modifications at 137 positions (8.7% in 1575 nucleobases) in 22 species of human mt-tRNAs. An up-to-date list of 34 genes responsible for mt-tRNA modifications are provided. We identify two genes required for queuosine (Q) formation in mt-tRNAs. Our results provide insight into the molecular mechanisms underlying the decoding system and could help to elucidate the molecular pathogenesis of human mitochondrial diseases caused by aberrant tRNA modifications.