Neural Regeneration Research ›› 2020, Vol. 15 ›› Issue (2): 212-221.doi: 10.4103/1673-5374.265560

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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).

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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