title: The RNA binding of protein A from Wuhan nodavirus is mediated by mitochondrial membrane lipids.
abstract: RNA replication of positive-strand (+)RNA viruses requires the lipids present in intracellular membranes, the sites of which viral replicases associate with. However, the direct effects of membrane lipids on viral replicases are still poorly understood. Wuhan nodavirus (WhNV) protein A, which associates with mitochondrial membranes, is the sole replicase required for RNA replication. Here, we report that WhNV protein A binds to RNA1 in a cooperative manner. Moreover, mitochondrial membrane lipids (MMLs) stimulated the RNA binding activity and cooperativity of protein A, and such stimulations exhibited strong selectivity for distinct phospholipids. Interestingly, MMLs stimulated the RNA-binding cooperativity only at higher protein A concentrations. Further investigation showed that MMLs stimulate the RNA binding of protein A by promoting its self-interaction. Finally, manipulating MML metabolism affected the protein A-induced RNA1 recruitment in cells. Together, our findings reveal the direct effects of membrane lipids on the RNA binding activity of a nodaviral replicase.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Miao
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Zhaowei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Cheng-Feng
authors.initials: CF
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Yuanyang
authors.initials: Y
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China. Electronic address: zhouxi@whu.edu.cn.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhou
mesh_terms: D054884:Host-Pathogen Interactions; D050356:Lipid Metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism*; D030381:Nodaviridae / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D016601:RNA-Binding Proteins; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase
keywords: Mitochondrial membrane lipids; Protein A; RNA binding; Wuhan Nodavirus
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