The coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an ongoing global public crisis. Although viral RNA modification has been reported based on the transcriptome architecture, the types and functions of RNA modification are still unknown. In this study, we evaluated the roles of RNA N6-methyladenosine (m6A) modification in SARS-CoV-2. Our methylated RNA immunoprecipitation sequencing (MeRIP-Seq) analysis showed that SARS-CoV-2 RNA contained m6A modification. Moreover, SARS-CoV-2 infection not only increased the expression of methyltransferase-like 3 (METTL3) but also altered its distribution. Modification of METTL3 expression by short hairpin RNA or plasmid transfection for knockdown or overexpression, respectively, affected viral replication. Furthermore, the viral key protein RdRp interacted with METTL3, and METTL3 was distributed in both the nucleus and cytoplasm in the presence of RdRp. RdRp appeared to modulate the sumoylation and ubiquitination of METTL3 via an unknown mechanism. Taken together, our findings demonstrated that the host m6A modification complex interacted with viral proteins to modulate SARS-CoV-2 replication.

中文翻译：

---

甲基转移酶样3调节严重急性呼吸系统综合症冠状病毒2 RNA N6-甲基腺苷修饰和复制

由严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）引起的2019年冠状病毒大流行是持续的全球公共危机。尽管已经报道了基于转录组结构的病毒RNA修饰，但是RNA修饰的类型和功能仍然未知。在这项研究中，我们评估了RNA N6-甲基腺苷（m6A）修饰在SARS-CoV-2中的作用。我们的甲基化RNA免疫沉淀测序（MeRIP-Seq）分析表明，SARS-CoV-2 RNA含有m6A修饰。此外，SARS-CoV-2感染不仅增加了甲基转移酶样3（METTL3）的表达，而且改变了其分布。分别通过短发夹RNA或质粒转染的敲低或过表达修饰METTL3表达会影响病毒复制。此外，病毒关键蛋白RdRp与METTL3相互作用，在存在RdRp的情况下METTL3分布在细胞核和细胞质中。RdRp似乎是通过未知机制来调节METTL3的合成和泛素化。综上所述，我们的发现表明宿主m6A修饰复合体与病毒蛋白相互作用以调节SARS-CoV-2复制。