Tian Haihua, Hu Zhenyu, Wang Chuang
1Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, Ningbo, Zhejiang, China.
2Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
Aging Dis. 2022 Apr 1;13(2):389-401. doi: 10.14336/AD.2021.0903. eCollection 2022 Apr.
Gene expressions and functions at various levels, namely post-transcriptional, transcriptional, and epigenetic, can be regulated by RNA (tRNA)-derived small RNAs (tsRNAs), which are as well-established as tRNA fragments or tRFs. This regulation occurs when tsRNAs are created through the special endonuclease-mediated cleavage of mature or precursor tRNAs. However, tsRNAs are newly discovered entities, and molecular functions associated with tsRNAs are still not clearly understood. There is increasingly robust evidence suggesting that specific tsRNAs perform fundamental tasks in the pathogenesis of neurodevelopmental, neurodegenerative, and neurobehavioral disorders. Indeed, the patterns of tsRNA expression are uncertain and could be altered in patients suffering from Parkinson's disease, pontocerebellar hypoplasia, amyotrophic lateral sclerosis, Alzheimer's disease, and other neurodegenerative disorders. In the present article, a review is conducted of recent domestic and international progress in research on the potential cellular and molecular mechanisms of tsRNA biogenesis. We also describe endogenous tsRNAs during neuronal development and neurodegenerative disorders, thereby providing theoretical support and guidance for further revealing the therapeutic potential of tsRNAs in neurodegenerative disorders.
基因在转录后、转录和表观遗传等各个水平的表达和功能，可由RNA（tRNA）衍生的小RNA（tsRNA）调控，tsRNA与tRNA片段或tRF一样已得到充分证实。当tsRNA通过特殊的核酸内切酶介导的成熟或前体tRNA切割产生时，就会发生这种调控。然而，tsRNAs是新发现的实体，与之相关的分子功能仍未完全清楚。越来越多有力的证据表明，特定的tsRNAs在神经发育、神经退行性和神经行为障碍的发病机制中发挥着基本作用。事实上，tsRNA的表达模式尚不确定，在帕金森病、脑桥小脑发育不全、肌萎缩侧索硬化症、阿尔茨海默病和其他神经退行性疾病患者中可能会发生改变。在本文中，我们综述了国内外关于tsRNA生物合成潜在细胞和分子机制的研究进展。我们还描述了神经元发育和神经退行性疾病中的内源性tsRNAs，从而为进一步揭示tsRNAs在神经退行性疾病中的治疗潜力提供理论支持和指导。
