Msi2-mediated MiR7a-1 processing repression promotes myogenesis

doi:10.1002/jcsm.12882

	Msi2-mediated MiR7a-1 processing repression promotes myogenesis
	Yang, Wenjun 1; Yang, Lele 2,3; Wang, Jianhua 4; Zhang, Yuanyuan 5; Li, Sheng 1; Yin, Qi 5; Suo, Jinlong 6,7; Ma, Ruimiao 2,3; Ye, Yuzhen 2,3; Cheng, Hong 5; Li, Jinsong8,9 ; Hui, Jingyi 5; Hu, Ping 1,2,3,10
	2022-02
发表期刊	JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE (IF:9.4[JCR-2023],10.6[5-Year])
ISSN	2190-5991
EISSN	2190-6009
发表状态	已发表
DOI	10.1002/jcsm.12882
摘要	Background Most of the microRNAs (MiRs) involved in myogenesis are transcriptional regulated. The role of MiR biogenesis in myogenesis has not been characterized yet. RNA-binding protein Musashi 2 (Msi2) is considered to be one of the major drivers for oncogenesis and stem cell proliferation. The functions of Msi2 in myogenesis have not been explored yet. We sought to investigate Msi2-regulated biogenesis of MiRs in myogenesis and muscle stem cell (MuSC) ageing. Methods We detected the expression of Msi2 in MuSCs and differentiated myotubes by quantitative reverse transcription PCR (RT-qPCR) and western blot. Msi2-binding partner human antigen R (HuR) was identified by immunoprecipitation followed by mass spectrometry analysis. The cooperative binding of Msi2 and HuR on MiR7a-1 was analysed by RNA immunoprecipitation and electrophoresis mobility shift assays. The inhibition of the processing of pri-MiR7a-1 mediated by Msi2 and HuR was shown by Msi2 and HuR knockdown. Immunofluorescent staining, RT-qPCR and immunoblotting were used to characterize the function of MiR7a-1 in myogenesis. Msi2 and HuR up-regulate cryptochrome circadian regulator 2 (Cry2) via MiR7a-1 was confirmed by the luciferase assay and western blot. The post-transcriptional regulatory cascade was further confirmed by RNAi and overexpressing of Msi2 and HuR in MuSCs, and the in vivo function was characterized by histopathological and molecular biological methods in Msi2 knockout mice. Results We identified a post-transcription regulatory cascade governed by a pair of RNA-binding proteins Msi2 and HuR. Msi2 is enriched in differentiated muscle cells and promotes MuSC differentiation despite its pro-proliferation functions in other cell types. Msi2 works synergistically with another RNA-binding protein HuR to repress the biogenesis of MiR7a-1 in an Msi2 dose-dependent manner to regulate the translation of the key component of the circadian core oscillator complex Cry2. Down-regulation of Cry2 (0.6-fold, vs. control, P < 0.05) mediated by MiR7a-1 represses MuSC differentiation. The disruption of this cascade leads to differentiation defects of MuSCs. In aged muscles, Msi2 (0.3-fold, vs. control, P < 0.01) expression declined, and the Cry2 protein level also decreases (0.5-fold, vs. control, P < 0.05), suggesting that the disruption of the Msi2-mediated post-transcriptional regulatory cascade could attribute to the declined ability of muscle regeneration in aged skeletal muscle. Conclusions Our findings have identified a new post-transcriptional cascade regulating myogenesis. The cascade is disrupted in skeletal muscle ageing, which leads to declined muscle regeneration ability.
关键词	Msi2 HuR MiR7a-1 processing Myogenesis Skeletal muscle ageing
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收录类别	SCI ; SCIE
语种	英语
资助项目	Strategic Priority Research Program of the Chinese Academy of Science[XDA16020400] ; Ministry of Science and Technology of China[2017YFA0102700] ; National Natural Science Foundation of China[32170804,81200355] ; CAS-Youth Innovation Program Association[2016246] ; Shanghai Natural Science Foundation[18ZR1446300]
WOS研究方向	Geriatrics & Gerontology ; General & Internal Medicine
WOS类目	Geriatrics & Gerontology ; Medicine, General & Internal
WOS记录号	WOS:000730321300001
出版者	WILEY
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/138718
专题	生命科学与技术学院_特聘教授组_李劲松组
通讯作者	Hui, Jingyi; Hu, Ping
作者单位	1.Shanghai Jiao Tong Univ, Sch Med, Xin Hua Hosp, Dept Pediat Orthoped, Shanghai, Peoples R China 2.Guangzhou Lab, Guangzhou, Peoples R China 3.Max Planck Ctr Tissue Stem Cells & Regenerat Med, Bioland Lab, Guangzhou 510320, Peoples R China 4.Shanghai Jiao Tong Univ, Sch Med, Xin Hua Hosp, Dept Orthopaed Surg, Shanghai, Peoples R China 5.Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China 6.Shanghai Haotong Univ, Affiliated Hosp 6, Dept Orthoped Surg, Shanghai, Peoples R China 7.Shanghai Haotong Univ, Affiliated Hosp 6, Inst Microsurg Extrem, Shanghai, Peoples R China 8.Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Mol Biol,Shanghai Key Lab Mol Andro, Shanghai, Peoples R China 9.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 10.Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Yang, Wenjun,Yang, Lele,Wang, Jianhua,et al. Msi2-mediated MiR7a-1 processing repression promotes myogenesis[J]. JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE,2022.
APA	Yang, Wenjun.,Yang, Lele.,Wang, Jianhua.,Zhang, Yuanyuan.,Li, Sheng.,...&Hu, Ping.(2022).Msi2-mediated MiR7a-1 processing repression promotes myogenesis.JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE.
MLA	Yang, Wenjun,et al."Msi2-mediated MiR7a-1 processing repression promotes myogenesis".JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE (2022).