N4-acetylcytidine regulates the replication and pathogenicity of enterovirus 71.
N4-acetylcytidine regulates the replication and pathogenicity of enterovirus 71.
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DOI：
10.1093/nar/gkac675
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发表时间：
2022-09-09
影响因子：
14.9
通讯作者：
Guan, Wuxiang
中科院分区：
文献类型：
--
作者：
Hao, Haojie;Liu, Weichi;Miao, Yuanjiu;Ma, Li;Yu, Baocheng;Liu, Lishi;Yang, Chunjie;Zhang, Kui;Chen, Zhen;Yang, Jingwen;Zheng, Zhenhua;Zhang, Bo;Deng, Fei;Gong, Peng;Yuan, Jianhui;Hu, Zhangli;Guan, Wuxiang
化学修饰对RNA的功能和代谢很重要。N4-乙酰胞苷（ac 4C）对mRNA的翻译和稳定性至关重要。虽然ac 4C存在于RNA病毒中，但ac 4C影响病毒复制的详细机制尚不清楚。在这里，我们报告了肠道病毒71（EV 71）基因组的5 '非翻译区被宿主乙酰转移酶NAT 10修饰为ac 4C。抑制NAT 10和内部核糖体进入位点（IRES）内的ac 4C位点的突变抑制了EV 71的复制。ac 4C通过选择性募集PCBP 2至IRES来增强病毒RNA翻译并提高RNA稳定性。此外，ac 4C增加了RNA依赖性RNA聚合酶（3D）与病毒RNA的结合。值得注意的是，ac 4C缺陷型EV 71在体内显示出降低的致病性。我们的研究结果强调了ac 4C在EV 71感染中的重要作用，并为潜在的抗病毒治疗提供了见解。
Chemical modifications are important for RNA function and metabolism. N4-acetylcytidine (ac4C) is critical for the translation and stability of mRNA. Although ac4C is found in RNA viruses, the detailed mechanisms through which ac4C affects viral replication are unclear. Here, we reported that the 5′ untranslated region of the enterovirus 71 (EV71) genome was ac4C modified by the host acetyltransferase NAT10. Inhibition of NAT10 and mutation of the ac4C sites within the internal ribosomal entry site (IRES) suppressed EV71 replication. ac4C enhanced viral RNA translation via selective recruitment of PCBP2 to the IRES and boosted RNA stability. Additionally, ac4C increased the binding of RNA-dependent RNA polymerase (3D) to viral RNA. Notably, ac4C-deficient mutant EV71 showed reduced pathogenicity in vivo. Our findings highlighted the essential role of ac4C in EV71 infection and provided insights into potential antiviral treatments.
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影响因子：
16.6
作者：
Balmus G;Larrieu D;Barros AC;Collins C;Abrudan M;Demir M;Geisler NJ;Lelliott CJ;White JK;Karp NA;Atkinson J;Kirton A;Jacobsen M;Clift D;Rodriguez R;Sanger Mouse Genetics Project;Adams DJ;Jackson SP
通讯作者：
Jackson SP
影响因子：
30.3
作者：
Kennedy EM;Bogerd HP;Kornepati AV;Kang D;Ghoshal D;Marshall JB;Poling BC;Tsai K;Gokhale NS;Horner SM;Cullen BR
通讯作者：
Cullen BR
影响因子：
16
作者：
Arango, Daniel;Sturgill, David;Yang, Renbin;Kanai, Tapan;Bauer, Paulina;Roy, Jyoti;Wang, Ziqiu;Hosogane, Masaki;Schiffers, Sarah;Oberdoerffer, Shalini
通讯作者：
Oberdoerffer, Shalini
影响因子：
13.2
作者：
Ang PY;Chong CWH;Alonso S
通讯作者：
Alonso S
影响因子：
4.4
作者：
Chen, Honghe;Pei, Rongjuan;Chen, Xinwen
通讯作者：
Chen, Xinwen