A complete landscape of post-transcriptional modifications in mammalian mitochondrial tRNAs.

A complete landscape of post-transcriptional modifications in mammalian mitochondrial tRNAs.
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DOI:
10.1093/nar/gku390
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发表时间:
2014-06
影响因子:
14.9
通讯作者:
Suzuki T
Suzuki T
中科院分区:
生物学2区
文献类型:
--
作者:
Suzuki T;Suzuki T

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在哺乳动物线粒体中,线粒体DNA编码的22种trna在参与氧化磷酸化的呼吸链复合物的13个基本亚基的翻译中起着至关重要的作用。转录后,线粒体trna被核编码的trna修饰酶修饰。这些修饰是线粒体trna (mt trna)正常运作所必需的,缺乏这些修饰会导致病理后果。然而,到目前为止,关于这些修改的信息是不完整的。为了解决这一问题,我们从牛肝脏中分离了所有22种mt tRNA,并通过质谱法全面测定了每种tRNA的转录后修饰。在这里,我们描述了7种mt trna的转录后修饰的主要结构,这些结构以前未被表征,并提供了关于其他5种mt trna的碱基修饰的修订信息。在完整的牛mt tRNAs序列中,我们在118个位置发现了15种修饰的核苷(占总碱基的7.48%)。这一结果提供了对哺乳动物线粒体解码系统的分子机制的深入了解,并使预测负责mt trna每种修饰的候选trna修饰酶成为可能。
In mammalian mitochondria, 22 species of tRNAs encoded in mitochondrial DNA play crucial roles in the translation of 13 essential subunits of the respiratory chain complexes involved in oxidative phosphorylation. Following transcription, mitochondrial tRNAs are modified by nuclear-encoded tRNA-modifying enzymes. These modifications are required for the proper functioning of mitochondrial tRNAs (mt tRNAs), and the absence of these modifications can cause pathological consequences. To date, however, the information available about these modifications has been incomplete. To address this issue, we isolated all 22 species of mt tRNAs from bovine liver and comprehensively determined the post-transcriptional modifications in each tRNA by mass spectrometry. Here, we describe the primary structures with post-transcriptional modifications of seven species of mt tRNAs which were previously uncharacterized, and provide revised information regarding base modifications in five other mt tRNAs. In the complete set of bovine mt tRNAs, we found 15 species of modified nucleosides at 118 positions (7.48% of total bases). This result provides insight into the molecular mechanisms underlying the decoding system in mammalian mitochondria and enables prediction of candidate tRNA-modifying enzymes responsible for each modification of mt tRNAs.
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