The nonstructural protein 2C of Coxsackie B virus has RNA helicase and chaperoning activities

Ziyu Chen; Xiaobei Xiong; Yiyang Li; Muhan Huang; Yujie Ren; Di Wu; Yang Qiu; Mingzhou Chen; Ting Shu; Xi Zhou

doi:10.1016/j.virs.2022.05.004

October 2022

. doi: 10.1016/j.virs.2022.05.004

Citation: Ziyu Chen, Xiaobei Xiong, Yiyang Li, Muhan Huang, Yujie Ren, Di Wu, Yang Qiu, Mingzhou Chen, Ting Shu, Xi Zhou. The nonstructural protein 2C of Coxsackie B virus has RNA helicase and chaperoning activities .VIROLOGICA SINICA, 2022, 37(5) : 656-663. http://dx.doi.org/10.1016/j.virs.2022.05.004

柯萨奇B型病毒非结构蛋白2C的解旋酶与RNA分子伴侣活性研究

陈紫玉 ^a,b ,
熊晓蓓 ^b ,
李依洋 ^b,c ,
黄霂晗 ^b ,
任玉洁 ^b ,
吴迪 ^b ,
邱洋 ^b,c ,
陈明周 ^a,, ,
舒婷 ^b,, ,
周溪 ^a,b,c,,

a 武汉大学生命科学学院国家重点实验室;
b 中国科学院武汉病毒研究所病毒学重点实验室;
c 中国科学院大学

通讯作者： 陈明周, chenmz@whu.edu.cn; 舒婷, shuting@wh.iov.cn; 周溪, zhouxi@wh.iov.cn
收稿日期： 2022-03-30
录用日期： 2022-05-10

摘要

RNA重塑蛋白，包括RNA解旋酶和RNA分子伴侣。在病毒复制过程中，RNA重塑蛋白能够帮助病毒RNA正确折叠和/或重新折叠。柯萨奇病毒B3（CVB3）和柯萨奇病毒B5（CVB5）属于微小核糖核酸病毒科的肠道病毒属，可引起包括手足口病、无菌性脑膜炎和病毒性心肌炎在内的多种传染病。在这项研究中，我们发现CVB3和CVB5的2C蛋白含有SF3家族经典解旋酶的保守基序A、B和C，经过实验证明2C既能作为RNA解旋酶以NTP依赖的模式双向解旋RNA，又能作为RNA分子伴侣以非NTP依赖的模式重塑RNA并促进RNA链退火。此外，我们的研究发现CVB3和CVB5 2C蛋白的NTPase活性和RNA解旋酶活性依赖于二价金属离子。我们的研究结果表明，柯萨奇B型病毒的2C蛋白具有RNA重塑蛋白活性，并强调了2C蛋白在柯萨奇B型病毒生命周期中的重要性。
- 2C蛋白
- , 柯萨奇病毒B3
- , 柯萨奇病毒B5
- , NTPase
- , RNA解旋酶
- , RNA分子伴侣

The nonstructural protein 2C of Coxsackie B virus has RNA helicase and chaperoning activities

Ziyu Chen ^a,b ,
Xiaobei Xiong ^b ,
Yiyang Li ^b,c ,
Muhan Huang ^b ,
Yujie Ren ^b ,
Di Wu ^b ,
Yang Qiu ^b,c ,
Mingzhou Chen ^a,, ,
Ting Shu ^b,, ,
Xi Zhou ^a,b,c,,

a State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China;
b State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China;
c University of Chinese Academy of Sciences, Beijing, 100081, China

Corresponding author: Mingzhou Chen, chenmz@whu.edu.cn Ting Shu, shuting@wh.iov.cn Xi Zhou, zhouxi@wh.iov.cn
Received Date: 30 March 2022
Accepted Date: 10 May 2022

Abstract

RNA-remodeling proteins, including RNA helicases and chaperones, play vital roles in the remodeling of structured RNAs. During viral replication, viruses require RNA-remodeling proteins to facilitate proper folding and/or re-folding the viral RNA elements. Coxsackieviruses B3 (CVB3) and Coxsackieviruses B5 (CVB5), belonging to the genus Enterovirus in the family Picornaviridae, have been reported to cause various infectious diseases such as hand-foot-and-mouth disease, aseptic meningitis, and viral myocarditis. However, little is known about whether CVB3 and CVB5 encode any RNA remodeling proteins. In this study, we showed that 2C proteins of CVB3 and CVB5 contained the conserved SF3 helicase A, B, and C motifs, and functioned not only as RNA helicase that unwound RNA helix bidirectionally in an NTP-dependent manner, but also as RNA chaperone that remodeled structured RNAs and facilitated RNA strand annealing independently of NTP. In addition, we determined that the NTPase activity and RNA helicase activity of 2C proteins of CVB3 and CVB5 were dependent on the presence of divalent metallic ions. Our findings demonstrate that 2C proteins of CVBs possess RNA-remodeling activity and underline the functional importance of 2C protein in the life cycle of CVBs.
- 2C protein
- , Coxsackieviruses B3 (CVB3)
- , Coxsackieviruses B5 (CVB5)
- , NTPase
- , RNA helicase
- , RNA chaperon

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Electronic Supplementary Material

10.1016j.virs.2022.05.004-ESM.docx