中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (2): 386-394.doi: 10.4103/1673-5374.314315

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

全基因组探查创伤性脑损伤模型小鼠转运RNA的小RNA的作用机制

  

  • 出版日期:2022-02-15 发布日期:2021-10-08

Genome-wide interrogation of transfer RNA-derived small RNAs in a mouse model of traumatic brain injury

Xiao-Jian Xu1, Meng-Shi Yang1, 2, Bin Zhang1, 2, Qian-Qian Ge1, 2, Fei Niu1, Jin-Qian Dong1, 2, Yuan Zhuang1, 2, Bai-Yun Liu1, 2, 3, 4, *#br#   

  1. 1Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China; 2Beijing Key Laboratory of Central Nervous System Injury and Department of Neurosurgery, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing, China; 3Nerve Injury and Repair Center of Beijing Institute for Brain Disorders, Beijing, China; 4China National Clinical Research Center for Neurological Diseases, Beijing, China
  • Online:2022-02-15 Published:2021-10-08
  • Contact: Bai-Yun Liu, MD, liubaiyun1212@163.com.
  • Supported by:
    This work was supported by grants from the National Natural Science Foundation of China, Nos. 81471238, 81771327; and Construction of Central Nervous System Injury Basic Science and Clinical Translational Research Platform, Budget of Beijing Municipal Health Commission 2020, No. PXM2020_026280_000002 (all to BYL). 

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摘要：

来源于转运RNA的小RNA （tsRNA）是一种新发现的调节性小RNA，可参与多种生物学过程。越来越多的研究表明，tsRNA的异常可导致神经功能的紊乱，且在神经退行性疾病中发挥一定的作用，然而其是否也参与到创伤性脑损伤诱发的继发性损伤并不明了。为此，实验以控制性脑皮质撞击法建立创伤性脑损伤模型，采用整合的tsRNA和mRNA转录组测序进行分析。结果可见，与正常小鼠相比，损伤后72h小鼠大脑皮质中有103种tsRNA存在差异表达，其中56种上调，而47种下调。基于miRNA样的种子匹配机制，并通过Pearson相关性分析，鉴定出57种差异表达的tsRNA-mRNA相互作用对，其中包含29种tsRNA和26种mRNA。此外，靶基因的基因本体注释揭示了显著丰富术语主要与炎症和突触功能有关。由此说明tsRNA可能与创伤性脑损伤诱发的继发性脑损伤有关，且可能成为创伤性脑损伤治疗的潜在靶点。实验于2019年4月11日经北京神经外科研究所动物伦理委员会批准（批准号20190411）。

https://orcid.org/0000-0001-8204-2623 (Bai-Yun Liu)

关键词: 创伤性脑损伤, 源自转移RNA的小RNA, 突触功能, 炎症, 下一代测序, 继发性损伤, 基因集富集分析, 转运RNA, 神经退行性疾病, 综合分析

Abstract: Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are a recently established family of regulatory small non-coding RNAs that modulate diverse biological processes. Growing evidence indicates that tsRNAs are involved in neurological disorders and play a role in the pathogenesis of neurodegenerative disease. However, whether tsRNAs are involved in traumatic brain injury-induced secondary injury remains poorly understood. In this study, a mouse controlled cortical impact model of traumatic brain injury was established, and integrated tsRNA and messenger RNA (mRNA) transcriptome sequencing were used. The results revealed that 103 tsRNAs were differentially expressed in the mouse model of traumatic brain injury at 72 hours, of which 56 tsRNAs were upregulated and 47 tsRNAs were downregulated. Based on microRNA-like seed matching and Pearson correlation analysis, 57 differentially expressed tsRNA-mRNA interaction pairs were identified, including 29 tsRNAs and 26 mRNAs. Moreover, Gene Ontology annotation of target genes revealed that the significantly enriched terms were primarily associated with inflammation and synaptic function. Collectively, our findings suggest that tsRNAs may be associated with traumatic brain injury-induced secondary brain injury, and are thus a potential therapeutic target for traumatic brain injury. The study was approved by the Beijing Neurosurgical Institute Animal Care and Use Committee (approval No. 20190411) on April 11, 2019.

Key words: gene set enrichment analysis, inflammation, integrated analysis, neurodegenerative disease, next-generation sequencing, secondary injury, synaptic function, transfer RNA-derived small RNAs, transfer RNAs, traumatic brain injury

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