Nuclear miR-30b-5p suppresses TFEB-mediated lysosomal biogenesis and autophagy

doi:10.1038/s41418-020-0602-4

	Nuclear miR-30b-5p suppresses TFEB-mediated lysosomal biogenesis and autophagy
	Guo, Huijie1,2,3 ; Pu, Mei1,2,3 ; Tai, Yusi 1,3; Chen, Yuxiang 1,3; Lu, Henglei 1,3; Qiao, Junwen 1,3; Wang, Guanghui 4,5; Chen, Jing 1; Qi, Xinming 1; Huang, Ruimin 1,3; Tao, Zhouteng 1,6; Ren, Jin1,2,3
	2021-01
发表期刊	CELL DEATH AND DIFFERENTIATION (IF:13.7[JCR-2023],13.7[5-Year])
ISSN	1350-9047
EISSN	1476-5403
发表状态	已发表
DOI	10.1038/s41418-020-0602-4
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.
收录类别	SCI ; SCIE
语种	英语
资助项目	National Natural Science Foundation of China[81701261][81771890] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program," China[2018ZX09101001-003-007][2018ZX09201017-004][2019ZX09732002-013][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][SIMM2004KF-02] ; Shanghai Committee of Science and Technology of China[18DZ2290200]
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Cell Biology
WOS记录号	WOS:000556619400001
出版者	NATURE PUBLISHING GROUP
WOS关键词	MICRORNAS ; EXPRESSION ; TARGET ; MECHANISM ; TRANSPORT ; GENOME
原始文献类型	Article ; Early Access
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/122952
专题	生命科学与技术学院_博士生生命科学与技术学院_特聘教授组_任进组生命科学与技术学院_硕士生
通讯作者	Huang, Ruimin; Tao, Zhouteng; Ren, Jin
作者单位	1.Chinese Acad Sci, Ctr Drug Safety Evaluat & Res, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 3.Univ Chinese Acad Sci, Beijing, Peoples R China 4.Soochow Univ, Coll Pharmaceut, Jiangsu Key Lab Neuropsychiat Dis, Lab Mol Neuropathol, Suzhou, Peoples R China 5.Soochow Univ, Coll Pharmaceut, Dept Pharmacol, Suzhou, Peoples R China 6.Chinese Acad Sci, Xian Inst Opt & Precis Mech, State Key Lab Transient Opt & Photon, Xian, Peoples R China
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
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,2021.
APA	Guo, Huijie.,Pu, Mei.,Tai, Yusi.,Chen, Yuxiang.,Lu, Henglei.,...&Ren, Jin.(2021).Nuclear miR-30b-5p suppresses TFEB-mediated lysosomal biogenesis and autophagy.CELL DEATH AND DIFFERENTIATION.
MLA	Guo, Huijie,et al."Nuclear miR-30b-5p suppresses TFEB-mediated lysosomal biogenesis and autophagy".CELL DEATH AND DIFFERENTIATION (2021).