NRDE2 negatively regulates exosome functions by inhibiting MTR4 recruitment and exosome interaction

doi:10.1101/gad.322602.118

	NRDE2 negatively regulates exosome functions by inhibiting MTR4 recruitment and exosome interaction
	Wang, Jianshu 1,2; Chen, Jiyun 3; Wu, Guifen 1,2; Zhang, Hongling 2,4; Du, Xian 5; Chen, Suli 1,2; Zhang, Li 1,2; Wang, Ke 1,2; Fan, Jing 1,2; Gao, Shuaixin 6
刊名	GENES & DEVELOPMENT
	2019-05-01
卷号	33 期号:9-10 页码:536-549
关键词	NRDE2 the nuclear exosome MTR4 recruitment mRNA export
ISSN号	0890-9369
DOI	10.1101/gad.322602.118
通讯作者	Zhou, Yu(yu.zhou@whu.edu.cn) ; Li, Jinsong(jsli@sibcb.ac.cn) ; Yun, Caihong(yunch@hsc.pku.edu.cn) ; Cheng, Hong(hcheng@sibcb.ac.cn)
英文摘要	The exosome functions in the degradation of diverse RNA species, yet how it is negatively regulated remains largely unknown. Here, we show that NRDE2 forms a 1:1 complex with MTR4, a nuclear exosome cofactor critical for exosome recruitment, via a conserved MTR4-interacting domain (MID). Unexpectedly, NRDE2 mainly localizes in nuclear speckles, where it inhibits MTR4 recruitment and RNA degradation, and thereby ensures efficient mRNA nuclear export. Structural and biochemical data revealed that NRDE2 interacts with MTR4's key residues, locks MTR4 in a closed conformation, and inhibits MTR4 interaction with the exosome as well as proteins important for MTR4 recruitment, such as the cap-binding complex (CBC) and ZFC3H1. Functionally, MID deletion results in the loss of self-renewal of mouse embryonic stem cells. Together, our data pinpoint NRDE2 as a nuclear exosome negative regulator that ensures mRNA stability and nuclear export.
资助项目	National Natural Science Foundation of China[31770880] ; National Natural Science Foundation of China[31570822] ; National Natural Science Foundation of China[31800686] ; National Key R&D Program of China[2017YFA0504400] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB19000000] ; National Science Foundation of China[31270769]
WOS关键词	CRYO-EM STRUCTURE ; NUCLEAR EXOSOME ; CRYSTAL-STRUCTURE ; QUALITY CONTROL ; MESSENGER-RNAS ; TREX COMPLEX ; ARCH DOMAIN ; HELICASE ; DEGRADATION ; PROTEIN
WOS研究方向	Cell Biology ; Developmental Biology ; Genetics & Heredity
语种	英语
出版者	COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
WOS记录号	WOS:000466358800006
资助机构	National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; National Science Foundation of China ; National Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; National Science Foundation of China ; National Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; National Science Foundation of China ; National Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; National Science Foundation of China ; National Science Foundation of China
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/165502]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Zhou, Yu; Li, Jinsong; Yun, Caihong; Cheng, Hong
作者单位	1.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci,State Key Lab Mol, Shanghai 200031, Peoples R China 2.Univ Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci,Shanghai Key Lab, Shanghai 200031, Peoples R China 3.Peking Univ Hlth Sci Ctr, Beijing Key Lab Tumor Syst Biol, Sch Basic Med Sci, Dept Biophys, Beijing 100191, Peoples R China 4.Univ Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci,State Key Lab Cel, Shanghai 200031, Peoples R China 5.Wuhan Univ, Coll Life Sci, Hubei Key Lab Cell Homeostasis, Wuhan 430072, Hubei, Peoples R China 6.Peking Univ Hlth Sci Ctr, Ctr Precis Med Multiom Res, Beijing 100191, Peoples R China 7.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Mol Modeling & Design, State Key Lab Mol React Dynam, Dalian 116023, Peoples R China 8.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
推荐引用方式 GB/T 7714	Wang, Jianshu,Chen, Jiyun,Wu, Guifen,et al. NRDE2 negatively regulates exosome functions by inhibiting MTR4 recruitment and exosome interaction[J]. GENES & DEVELOPMENT,2019,33(9-10):536-549.
APA	Wang, Jianshu.,Chen, Jiyun.,Wu, Guifen.,Zhang, Hongling.,Du, Xian.,...&Cheng, Hong.(2019).NRDE2 negatively regulates exosome functions by inhibiting MTR4 recruitment and exosome interaction.GENES & DEVELOPMENT,33(9-10),536-549.
MLA	Wang, Jianshu,et al."NRDE2 negatively regulates exosome functions by inhibiting MTR4 recruitment and exosome interaction".GENES & DEVELOPMENT 33.9-10(2019):536-549.