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转运RNA衍生的小RNA及其在心肌肥厚中的潜在作用

tRNA-Derived Small RNAs and Their Potential Roles in Cardiac Hypertrophy.

作者信息

Cao Jun, Cowan Douglas B, Wang Da-Zhi

机构信息

Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States.

出版信息

Front Pharmacol. 2020 Sep 17;11:572941. doi: 10.3389/fphar.2020.572941. eCollection 2020.

Abstract

Transfer RNAs (tRNAs) are abundantly expressed, small non-coding RNAs that have long been recognized as essential components of the protein translation machinery. The tRNA-derived small RNAs (tsRNAs), including tRNA halves (tiRNAs), and tRNA fragments (tRFs), were unexpectedly discovered and have been implicated in a variety of important biological functions such as cell proliferation, cell differentiation, and apoptosis. Mechanistically, tsRNAs regulate mRNA destabilization and translation, as well as retro-element reverse transcriptional and post-transcriptional processes. Emerging evidence has shown that tsRNAs are expressed in the heart, and their expression can be induced by pathological stress, such as hypertrophy. Interestingly, cardiac pathophysiological conditions, such as oxidative stress, aging, and metabolic disorders can be viewed as inducers of tsRNA biogenesis, which further highlights the potential involvement of tsRNAs in these conditions. There is increasing enthusiasm for investigating the molecular and biological functions of tsRNAs in the heart and their role in cardiovascular disease. It is anticipated that this new class of small non-coding RNAs will offer new perspectives in understanding disease mechanisms and may provide new therapeutic targets to treat cardiovascular disease.

摘要

转运RNA(tRNA)是大量表达的小非编码RNA,长期以来一直被认为是蛋白质翻译机制的重要组成部分。意外发现了源自tRNA的小RNA(tsRNA),包括tRNA半体(tiRNA)和tRNA片段(tRF),它们与多种重要生物学功能有关,如细胞增殖、细胞分化和细胞凋亡。从机制上讲,tsRNA调节mRNA的稳定性和翻译,以及逆转录元件的逆转录和转录后过程。新出现的证据表明,tsRNA在心脏中表达,其表达可由病理应激(如肥大)诱导。有趣的是,心脏病理生理状况,如氧化应激、衰老和代谢紊乱,可被视为tsRNA生物合成的诱导因素,这进一步凸显了tsRNA在这些状况中的潜在参与。人们对研究tsRNA在心脏中的分子和生物学功能及其在心血管疾病中的作用越来越感兴趣。预计这类新的小非编码RNA将为理解疾病机制提供新的视角,并可能为治疗心血管疾病提供新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a5d/7527594/156319730c24/fphar-11-572941-g001.jpg

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