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

• Published in: Virologica Sinica Vol. 37; no. 5; pp. 656 - 663
• Main Authors: Chen, Ziyu, Xiong, Xiaobei, Li, Yiyang, Huang, Muhan, Ren, Yujie, Wu, Di, Qiu, Yang, Chen, Mingzhou, Shu, Ting, Zhou, Xi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2022; Wuhan Institute of Virology, Chinese Academy of Sciences
• Subjects: 2C protein; Coxsackieviruses B3 (CVB3); Coxsackieviruses B5 (CVB5); NTPase; RNA chaperon; RNA helicase; Coxsackieviruses B3 (CVB3); Coxsackieviruses B5 (CVB5); NTPase; RNA chaperon; 2C protein; RNA helicase
• ISSN: 1995-820X; 1674-0769; 1995-820X
• DOI: 10.1016/j.virs.2022.05.004

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 proteins of CVB3 and CVB5 function as RNA helicase in an NTP-dependent manner.•2C proteins of CVB3 and CVB5 possess RNA-remodeling activity independently of NTP.•2C proteins may have functional significance in the life cycle of CVBs.