tRNA ‐derived small RNA, 5'tiRNA‐Gly‐CCC , promotes skeletal muscle regeneration through the inflammatory response

作者：Linyuan Shen, Tianci Liao, Qiuyang Chen, Yuhang Lei, Linghui Wang, Hao Gu, Yanhao Qiu, Ting Zheng, Yiting Yang, Chenggang Wei, Lei Chen, Ye Zhao, Lili Niu, Shunhua Zhang, Yan Zhu, Mingzhou Li, Jinyong Wang, Xuewei Li, Mailin Gan, Li Zhu · 发表于：Journal of Cachexia Sarcopenia and Muscle · 年份：2023 · DOI：10.1002/jcsm.13187 · 被引用次数：49 · 研究领域：RNA modifications and cancer、Muscle Physiology and Disorders、MicroRNA in disease regulation

Abstract Background Increasing evidence shows that tRNA‐derived small RNAs (tsRNAs) are not only by‐products of transfer RNAs, but they participate in numerous cellular metabolic processes. However, the role of tsRNAs in skeletal muscle regeneration remains unknown. Methods Small RNA sequencing revealed the relationship between tsRNAs and skeletal muscle injury. The dynamic expression level of 5'tiRNA‐Gly after muscle injury was confirmed by real‐time quantitative PCR (q‐PCR). In addition, q‐PCR, flow cytometry, the 5‐ethynyl‐2'‐deoxyuridine (Edu), cell counting kit‐8, western blotting and immunofluorescence were used to explore the biological function of 5'tiRNA‐Gly. Bioinformatics analysis and dual‐luciferase reporter assay were used to further explore the mechanism of action under the biological function of 5'tiRNA‐Gly. Results Transcriptome analysis revealed that tsRNAs were significantly enriched during inflammatory response immediately after muscle injury. Interestingly, we found that 5'tiRNA‐Gly was significantly up‐regulated after muscle injury ( P < 0.0001) and had a strong positive correlation with inflammation in vivo. In vitro experiments showed that 5'tiRNA‐Gly promoted the mRNA expression of proinflammatory cytokines ( IL‐1β , P = 0.0468; IL‐6 , P = 0.0369) and the macrophages of M1 markers ( TNF‐α , P = 0.0102; CD80 , P = 0.0056; MCP‐1 , P = 0.0002). On the contrary, 5'tiRNA‐Gly inhibited the mRNA expression of anti‐inflammatory cytokines ( IL‐4 , P = 0.0009...