College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China.
College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China.
Nucleic Acids Res. 2022 Sep 9;50(16):9339-9354. doi: 10.1093/nar/gkac675.
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.
化学修饰对于 RNA 的功能和代谢至关重要。N4-乙酰胞嘧啶 (ac4C) 对 mRNA 的翻译和稳定性至关重要。尽管 ac4C 存在于 RNA 病毒中，但 ac4C 影响病毒复制的详细机制尚不清楚。在这里，我们报道了肠道病毒 71（EV71）基因组的 5'非翻译区被宿主乙酰转移酶 NAT10 乙酰化修饰。抑制 NAT10 和突变内部核糖体进入位点（IRES）内的 ac4C 位点抑制 EV71 复制。ac4C 通过选择性募集 PCBP2 到 IRES 来增强病毒 RNA 翻译，并提高 RNA 稳定性。此外，ac4C 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，体内缺乏 ac4C 的突变型 EV71 显示出降低的致病性。我们的研究结果强调了 ac4C 在 EV71 感染中的重要作用，并为潜在的抗病毒治疗提供了思路。
