中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (2): 212-221.doi: 10.4103/1673-5374.265560

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tRNA衍生小RNA的生物学功能在神经系统疾病中的病理学意义

  

  • 出版日期:2020-02-15 发布日期:2020-05-23
  • 基金资助:
    国家自然科学基金(81870979,81271366); 中国国家重点研发计划(2018YFF0301104); 中国中央研究院基础科学研究专项基金(2018CZ-1); 中国康复研究中心基础科学研究基金(2018ZX-30); CRRC科学研究基金(2012C-1号); 中国北京市重大科技项目(D161100002816004); 中国特殊资本健康研究与发展项目(2018-1-6011)

Pathological significance of tRNA-derived small RNAs in neurological disorders

Chuan Qin1, 2, 3, 4, 5, Pei-Pei Xu1, 2, 3, 4, 5, Xin Zhang1, 2, 3, 4, 5, Chao Zhang1, 2, 3, 4, 5, Chang-Bin Liu1, 2, 3, 4, 5, De-Gang Yang1, 2, 3, 4, 5, Feng Gao1, 2, 3, 4, 5, Ming-Liang Yang1, 2, 3, 4, 5, Liang-Jie Du1, 2, 3, 4, 5, Jian-Jun Li1, 2, 3, 4, 5#br#   

  1. 1 School of Rehabilitation Medicine, Capital Medical University, Beijing, China
    2 China Rehabilitation Science Institute, Beijing, China
    3 Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
    4 Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
    5 Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
  • Online:2020-02-15 Published:2020-05-23
  • Contact: Jian-Jun Li, MS,crrclijj@163.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81870979 (to JJL), No. 81271366 (to MLY); the National Key R & D Program of China, No. 2018YFF0301104 (to JJL); the Special Fund for Basic Scientific Research of Central Public Research Institutes of China, No. 2018CZ-1 (to JJL); the Basic Scientific Research Foundation of China Rehabilitation Research Center, No. 2018ZX-30 (to FG); the Scientific Research Foundation of CRRC, No. 2012C-1 (to JJL); the Major Science and Technology Project of Beijing of China, No. D161100002816004 (to JJL); the Special Capital Health Research and Development of China, No. 2018-1-6011 (to JJL).

摘要:

非编码RNA(ncRNA)是一类不能被翻译成蛋白质的RNA。转移RNA(tRNA)是其中一种ncRNA,并且是细胞中含量第二丰富的RNA。最近的研究显示tRNA可以被切割裂解成长度为18-40个核苷酸的异质ncRNA群,称为tRNA来源的小RNA(tsRNA)。基于它们的长度和切割位点的数量,tsRNA可分为2种主要类型:tRNA衍生的片段(tRF)和tRNA衍生的应激诱导的RNA(tiRNA)。这些RNA最初被认为是tRNA随机切割的副产物。然而,越来越多的证据表明它们作为各种疾病(包括神经疾病)的关键调节因子,在病理生理过程中起着关键的功能作用。然而,tsRNA影响特定细胞过程的潜在机制在很大程度上是未知的。因此在这篇文章里,文章全面概述了以下几点:①tsRNA的生物发生学,包括tsRNA的发现,分类,形成过程及关键酶的作用;②tsRNA主要的生物学功能,包括;类似于miRNA的基因调控作用,调控蛋白质翻译,调节多种细胞活动,免疫调节,应激状态下的变化;③tsRNA调控神经系统疾病病理生理变化的潜在作用机制,包括神经退行性变和神经创伤。④文章认为,鉴定tsRNA的功能多样性将为神经障碍的生理学和病理生理学机制研究提供有价值的信息,从而为临床治疗神经系统疾病提供新的参考依据,但在神经系统疾病中关于tsRNA的研究也同时存在如下挑战:潜在功能和机制研究,如何精准量化表达;tsRNA和miRNA之间的确切关系等,这些需要我们在未来开展研究去证实。

orcid: 0000-0002-8441-7537 (Jian-Jun Li)

关键词: tRNA, tRNA衍生的片段, tRNA衍生的应激诱导的RNA, tRNA来源的小RNA, 神经系统疾病, 综述, 表观遗传学, 分子生物学, 应激, 测序

Abstract: Non-coding RNAs (ncRNAs) are a type of RNA that is not translated into proteins. Transfer RNAs (tRNAs), a type of ncRNA, are the second most abundant type of RNA in cells. Recent studies have shown that tRNAs can be cleaved into a heterogeneous population of ncRNAs with lengths of 18–40 nucleotides, known as tRNA-derived small RNAs (tsRNAs). There are two main types of tsRNA, based on their length and the number of cleavage sites that they contain: tRNA-derived fragments and tRNA-derived stress-induced RNAs. These RNA species were first considered to be byproducts of tRNA random cleavage. However, mounting evidence has demonstrated their critical functional roles as regulatory factors in the pathophysiological processes of various diseases, including neurological diseases. However, the underlying mechanisms by which tsRNAs affect specific cellular processes are largely unknown. Therefore, this study comprehensively summarizes the following points: (1) The biogenetics of tsRNA, including their discovery, classification, formation, and the roles of key enzymes. (2) The main biological functions of tsRNA, including its miRNA-like roles in gene expression regulation, protein translation regulation, regulation of various cellular activities, immune mediation, and response to stress. (3) The potential mechanisms of pathophysiological changes in neurological diseases that are regulated by tsRNA, including neurodegeneration and neurotrauma. (4) The identification of the functional diversity of tsRNA may provide valuable information regarding the physiological and pathophysiological mechanisms of neurological disorders, thus providing a new reference for the clinical treatment of neurological diseases. Research into tsRNAs in neurological diseases also has the following challenges: potential function and mechanism studies, how to accurately quantify expression, and the exact relationship between tsRNA and miRNA. These challenges require future research efforts.

Key words: epigenetics, molecular biology, neurological disorders, review, sequencing, stress, tRNA, tRNA-derived fragments, tRNA-derived small RNAs, tRNA-derived stress-induced RNA