中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Nuclear miR-30b-5p suppresses TFEB-mediated lysosomal biogenesis and autophagy

文献类型：期刊论文

作者Guo, Huijie3,4,5; Pu, Mei3,4,5; Tai, Yusi3,5; Chen, Yuxiang3,5; Lu, Henglei3,5; Qiao, Junwen3,5; Wang, Guanghui1,2; Chen, Jing3; Qi, Xinming3; Huang, Ruimin3,5
刊名CELL DEATH AND DIFFERENTIATION
出版日期2020-08-06
页码17
ISSN号1350-9047
DOI10.1038/s41418-020-0602-4
通讯作者Huang, Ruimin(rmhuang@simm.ac.cn) ; Tao, Zhouteng(tztboy@hotmail.com) ; Ren, Jin(jren@cdser.simm.ac.cn)
英文摘要Lysosome is a crucial organelle in charge of degrading proteins and damaged organelles to maintain cellular homeostasis. Transcription factor EB (TFEB) is the master transcription factor regulating lysosomal biogenesis and autophagy. Under external stimuli such as starvation, dephosphorylated TFEB transports into the nucleus to specifically recognize and bind to the coordinated lysosomal expression and regulation (CLEAR) elements at the promotors of autophagy and lysosomal biogenesis-related genes. The function of TFEB in the nucleus is fine regulated but the molecular mechanism is not fully elucidated. In this study, we discovered that miR-30b-5p, a small RNA which is known to regulate a series of genes through posttranscriptional regulation in the cytoplasm, was translocated into the nucleus, bound to the CLEAR elements, suppressed the transcription of TFEB-dependent downstream genes, and further inhibited the lysosomal biogenesis and the autophagic flux; meanwhile, knocking out the endogenous miR-30b-5p by CRISPR/Cas9 technique significantly increased the TFEB-mediated transactivation, resulting in the increased expression of autophagy and lysosomal biogenesis-related genes. Overexpressing miR-30b-5p in mice livers showed a decrease in lysosomal biogenesis and autophagy. These in vitro and in vivo data indicate that miR-30b-5p may inhibit the TFEB-dependent transactivation by binding to the CLEAR elements in the nucleus to regulate the lysosomal biogenesis and autophagy. This novel mechanism of nuclear miRNA regulating gene transcription is conducive to further elucidating the roles of miRNAs in the lysosomal physiological functions and helps to understand the pathogenesis of abnormal autophagy-related diseases.
WOS关键词MICRORNAS ; EXPRESSION ; TARGET ; MECHANISM ; TRANSPORT ; GENOME
资助项目National Natural Science Foundation of China[81701261] ; National Natural Science Foundation of China[81771890] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09101001-003-007] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09201017-004] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2019ZX09732002-013] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002-010-001] ; Open Research Fund of State Key Laboratory of Transient Optics and Photonics[SKLST201806] ; Fundamental and Open Research Funds from the State Key Laboratory of Drug Research[SIMM1903ZZ-05] ; Fundamental and Open Research Funds from the State Key Laboratory of Drug Research[SIMM2004KF-02] ; Shanghai Committee of Science and Technology of China[18DZ2290200]
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
WOS记录号WOS:000556619400001
出版者NATURE PUBLISHING GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/292288]  
专题新药研究国家重点实验室
通讯作者Huang, Ruimin; Tao, Zhouteng; Ren, Jin
作者单位1.Soochow Univ, Coll Pharmaceut, Jiangsu Key Lab Neuropsychiat Dis, Lab Mol Neuropathol, Suzhou, Peoples R China
2.Soochow Univ, Coll Pharmaceut, Dept Pharmacol, Suzhou, Peoples R China
3.Chinese Acad Sci, Ctr Drug Safety Evaluat & Res, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
5.Univ Chinese Acad Sci, Beijing, Peoples R China
6.Chinese Acad Sci, Xian Inst Opt & Precis Mech, State Key Lab Transient Opt & Photon, Xian, Peoples R China
推荐引用方式
GB/T 7714		 Guo, Huijie,Pu, Mei,Tai, Yusi,et al. Nuclear miR-30b-5p suppresses TFEB-mediated lysosomal biogenesis and autophagy[J]. CELL DEATH AND DIFFERENTIATION,2020:17.
APA Guo, Huijie.,Pu, Mei.,Tai, Yusi.,Chen, Yuxiang.,Lu, Henglei.,...&Ren, Jin.(2020).Nuclear miR-30b-5p suppresses TFEB-mediated lysosomal biogenesis and autophagy.CELL DEATH AND DIFFERENTIATION,17.
MLA Guo, Huijie,et al."Nuclear miR-30b-5p suppresses TFEB-mediated lysosomal biogenesis and autophagy".CELL DEATH AND DIFFERENTIATION (2020):17.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。