Binding of cellular nucleolin with the viral core RNA G-quadruplex structure suppresses HCV replication

doi:10.1093/nar/gky1177

	Binding of cellular nucleolin with the viral core RNA G-quadruplex structure suppresses HCV replication
	Zhang, Xiao-Lian 4,5,6; Zhou, Xiang 1; Long, Gang 3; Li, Shu 4,5,6; Fu, Bo-Shi 1; Xu, Guo-Hua 2; Wang, Xiao-Ning 3; Xie, Yan 4,5,6; Bian, Wen-Xiu 4,5,6
刊名	NUCLEIC ACIDS RESEARCH
	2019-01-10
卷号	47 期号:1 页码:56-68
ISSN号	0305-1048
DOI	10.1093/nar/gky1177
英文摘要	Hepatitis C virus (HCV) infection is a major cause of human chronic liver disease and hepatocellular carcinoma. G-quadruplex (G4) is an important four-stranded secondary structure of nucleic acids. Recently, we discovered that the core gene of HCV contains a G4 RNA structure; however, the interaction between the HCV core RNA G4 and host cellular proteins, and the roles of the HCV core RNA G4 in HCV infection and pathogenesis remain elusive. Here, we identified a cellular protein, nucleolin (NCL), which bound and stabilized the HCV core RNA G4 structure. We demonstrated the direct interaction and colocalization between NCL and wild-type core RNA G4 at both in vitro and in cell physiological conditions of the alive virus; however no significant interaction was found between NCL and G4-modified core RNA. NCL is also associated with HCV particles. HCV infection induced NCL mRNA and protein expression, while NCL suppressed wild-type viral replication and expression, but not G4-modified virus. Silencing of NCL greatly enhanced viral RNA replication. Our findings provide new insights that NCL may act as a host factor for anti-viral innate immunity, and binding of cellular NCL with the viral core RNA G4 structure is involved in suppressing HCV replication.
资助项目	National Key R&D Program of China[2018YFA0507603] ; National Natural Science Foundation of China[21572173] ; National Natural Science Foundation of China[91740120] ; National Natural Science Foundation of China[31370197] ; National Natural Science Foundation of China[21432008] ; National Natural Science Foundation of China[21721005] ; National Natural Science Foundation of China[91753201] ; National Outstanding Youth Foundation of China[81025008] ; Major Projects of Technological Innovation of Hubei Province[2016ACA150] ; Natural Science Foundation Project of Hunan Province[2016CFA062]
WOS关键词	HEPATITIS-C-VIRUS ; MYC G-QUADRUPLEX ; MESSENGER-RNA ; DNA ; PROMOTER ; PROTEIN ; IDENTIFICATION ; EXPRESSION ; INFECTION ; SELECTION
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	OXFORD UNIV PRESS
WOS记录号	WOS:000462586700012
资助机构	National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Outstanding Youth Foundation of China ; National Outstanding Youth Foundation of China ; Major Projects of Technological Innovation of Hubei Province ; Major Projects of Technological Innovation of Hubei Province ; Natural Science Foundation Project of Hunan Province ; Natural Science Foundation Project of Hunan Province ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Outstanding Youth Foundation of China ; National Outstanding Youth Foundation of China ; Major Projects of Technological Innovation of Hubei Province ; Major Projects of Technological Innovation of Hubei Province ; Natural Science Foundation Project of Hunan Province ; Natural Science Foundation Project of Hunan Province ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Outstanding Youth Foundation of China ; National Outstanding Youth Foundation of China ; Major Projects of Technological Innovation of Hubei Province ; Major Projects of Technological Innovation of Hubei Province ; Natural Science Foundation Project of Hunan Province ; Natural Science Foundation Project of Hunan Province ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Outstanding Youth Foundation of China ; National Outstanding Youth Foundation of China ; Major Projects of Technological Innovation of Hubei Province ; Major Projects of Technological Innovation of Hubei Province ; Natural Science Foundation Project of Hunan Province ; Natural Science Foundation Project of Hunan Province
内容类型	期刊论文
源URL	[http://ir.wipm.ac.cn/handle/112942/13912]
专题	中国科学院武汉物理与数学研究所
通讯作者	Zhang, Xiao-Lian; Zhou, Xiang
作者单位	1.Wuhan Univ, Coll Chem & Mol Sci, Wuhan 430072, Hubei, Peoples R China 2.Chinese Acad Sci, Wuhan Inst Phys & Math, Wuhan 430071, Hubei, Peoples R China 3.Chinese Acad Sci, Key Lab Mol Virol & Immunol, Inst Pasteur Shanghai, Shanghai Inst Biol Sci, Shanghai, Peoples R China 4.Wuhan Univ, Sch Basic Med Sci, Dept Immunol, Wuhan 430071, Peoples R China 5.Wuhan Univ, Sch Basic Med Sci, Hubei Prov Key Lab Allergy & Immunol, Med Res Inst, Wuhan 430071, Peoples R China 6.Wuhan Univ, Sch Basic Med Sci, State Key Lab Virol, Med Res Inst, Wuhan 430071, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Xiao-Lian,Zhou, Xiang,Long, Gang,et al. Binding of cellular nucleolin with the viral core RNA G-quadruplex structure suppresses HCV replication[J]. NUCLEIC ACIDS RESEARCH,2019,47(1):56-68.
APA	Zhang, Xiao-Lian.,Zhou, Xiang.,Long, Gang.,Li, Shu.,Fu, Bo-Shi.,...&Bian, Wen-Xiu.(2019).Binding of cellular nucleolin with the viral core RNA G-quadruplex structure suppresses HCV replication.NUCLEIC ACIDS RESEARCH,47(1),56-68.
MLA	Zhang, Xiao-Lian,et al."Binding of cellular nucleolin with the viral core RNA G-quadruplex structure suppresses HCV replication".NUCLEIC ACIDS RESEARCH 47.1(2019):56-68.