RNA m 6 A methylation regulates virus–host interaction and EBNA2 expression during Epstein–Barr virus infection

作者：Xiang Zheng, Jia Wang, Xiaoyue Zhang, Yuxin Fu, Peng Qiu, Jianhong Lu, Lingyu Wei, Zhengshuo Li, Can Liu, Yangge Wu, Qun Yan, Jian Ma · 发表于：Immunity Inflammation and Disease · 年份：2021 · DOI：10.1002/iid3.396 · 被引用次数：43 · 研究领域：RNA modifications and cancer、Viral-associated cancers and disorders、HVDC Systems and Fault Protection

Abstract Introduction N 6 ‐methyladenosine (m 6 A) is the most prevalent modification that occurs in messenger RNA (mRNA), affecting mRNA splicing, translation, and stability. This modification is reversible, and its related biological functions are mediated by “writers,” “erasers,” and “readers.” The field of viral epitranscriptomics and the role of m 6 A modification in virus–host interaction have attracted much attention recently. When Epstein–Barr virus (EBV) infects a human B lymphocyte, it goes through three phases: the pre‐latent phase, latent phase, and lytic phase. Little is known about the viral and cellular m 6 A epitranscriptomes in EBV infection, especially in the pre‐latent phase during de novo infection. Methods Methylated RNA immunoprecipitation sequencing (MeRIP‐seq) and MeRIP‐RT‐qPCR were used to determine the m 6 A‐modified transcripts during de novo EBV infection. RIP assay was used to confirm the binding of EBNA2 and m 6 A readers. Quantitative reverse‐transcription polymerase chain reaction (RT‐qPCR) and Western blot analysis were performed to test the effect of m 6 A on the host and viral gene expression. Results Here, we provided mechanistic insights by examining the viral and cellular m 6 A epitranscriptomes during de novo EBV infection, which is in the pre‐latent phase. EBV EBNA2 and BHRF1 were highly m 6 A‐modified upon EBV infection. Knockdown of METTL3 (a “writer”) decreased EBNA2 expression levels. The emergent m 6 A modifications induced by EBV ...