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tRNA 修饰的扩展世界及其与疾病的相关性。

The expanding world of tRNA modifications and their disease relevance.

机构信息

Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.

出版信息

Nat Rev Mol Cell Biol. 2021 Jun;22(6):375-392. doi: 10.1038/s41580-021-00342-0. Epub 2021 Mar 3.

DOI:10.1038/s41580-021-00342-0
PMID:33658722
Abstract

Transfer RNA (tRNA) is an adapter molecule that links a specific codon in mRNA with its corresponding amino acid during protein synthesis. tRNAs are enzymatically modified post-transcriptionally. A wide variety of tRNA modifications are found in the tRNA anticodon, which are crucial for precise codon recognition and reading frame maintenance, thereby ensuring accurate and efficient protein synthesis. In addition, tRNA-body regions are also frequently modified and thus stabilized in the cell. Over the past two decades, 16 novel tRNA modifications were discovered in various organisms, and the chemical space of tRNA modification continues to expand. Recent studies have revealed that tRNA modifications can be dynamically altered in response to levels of cellular metabolites and environmental stresses. Importantly, we now understand that deficiencies in tRNA modification can have pathological consequences, which are termed 'RNA modopathies'. Dysregulation of tRNA modification is involved in mitochondrial diseases, neurological disorders and cancer.

摘要

转移 RNA(tRNA)是一种衔接分子,在蛋白质合成过程中,它将 mRNA 中的特定密码子与其对应的氨基酸连接起来。tRNA 在转录后会发生酶促修饰。在 tRNA 的反密码子中发现了各种各样的 tRNA 修饰,这些修饰对于精确的密码子识别和阅读框维持至关重要,从而确保了蛋白质合成的准确性和高效性。此外,tRNA 体区也经常被修饰,从而在细胞中稳定下来。在过去的二十年中,在各种生物体中发现了 16 种新的 tRNA 修饰,并且 tRNA 修饰的化学空间还在不断扩大。最近的研究表明,tRNA 修饰可以根据细胞代谢物和环境应激的水平而动态改变。重要的是,我们现在知道,tRNA 修饰的缺陷可能会产生病理后果,这被称为“RNA 修饰病”。tRNA 修饰的失调与线粒体疾病、神经紊乱和癌症有关。

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Complete chemical structures of human mitochondrial tRNAs.人线粒体 tRNA 的完整化学结构。
Nat Commun. 2020 Aug 28;11(1):4269. doi: 10.1038/s41467-020-18068-6.
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Quantitative tRNA-sequencing uncovers metazoan tissue-specific tRNA regulation.定量 tRNA 测序揭示后生动物组织特异性 tRNA 调控。
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Chemically modified tRNA enhances the translation capacity of mRNA rich in cognate codons.化学修饰的转运RNA增强了富含同源密码子的信使RNA的翻译能力。
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