The nonstructural protein 2C of Coxsackie B virus has RNA helicase and chaperoning activities.
The nonstructural protein 2C of Coxsackie B virus has RNA helicase and chaperoning activities.
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DOI：
10.1016/j.virs.2022.05.004
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发表时间：
2022-10
影响因子：
5.5
通讯作者：
Zhou, Xi
中科院分区：
文献类型：
--
作者：
Chen, Ziyu;Xiong, Xiaobei;Li, Yiyang;Huang, Muhan;Ren, Yujie;Wu, Di;Qiu, Yang;Chen, Mingzhou;Shu, Ting;Zhou, Xi
RNA重塑蛋白包括RNA解旋酶和分子伴侣，在结构化RNA的重塑中起重要作用。在病毒复制过程中，病毒需要RNA重塑蛋白来促进病毒RNA元件的正确折叠和/或再折叠。柯萨奇病毒B3（Coxsackieviruses B3，CVB 3）和柯萨奇病毒B5（Coxsackieviruses B5，CVB 5）属于小核糖核酸病毒科肠道病毒属（Enterovirus），可引起手足口病、无菌性脑膜炎、病毒性心肌炎等多种传染病。然而，很少有人知道CVB 3和CVB 5是否编码任何RNA重塑蛋白。在这项研究中，我们发现CVB 3和CVB 5的2C蛋白包含保守的SF 3解旋酶A，B和C基序，不仅作为RNA解旋酶，以NTP依赖的方式双向解旋RNA螺旋，而且作为RNA分子伴侣，重塑结构RNA和促进RNA链退火独立于NTP。此外，我们确定了CVB 3和CVB 5的2C蛋白的NTR酶活性和RNA解旋酶活性依赖于二价金属离子的存在。我们的研究结果表明，2C蛋白的CVBs具有RNA重塑活性，并强调2C蛋白在CVBs的生活周期中的功能重要性。CVB 3和CVB 5的2C蛋白以NTP依赖的方式作为RNA解旋酶起作用。CVB 3和CVB 5的2C蛋白具有不依赖NTP的RNA重塑活性。2C蛋白在CVBs的生活史中可能具有重要的功能意义。
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.
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