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N(6)‐methyladenosine‐binding protein YTHDF1 suppresses EBV replication and promotes EBV RNA decay
Author(s) -
Xia TianLiang,
Li Xingyang,
Wang Xueping,
Zhu YunJia,
Zhang Hua,
Cheng Weisheng,
Chen MeiLing,
Ye Ying,
Li Yan,
Zhang Ao,
Dai DanLing,
Zhu QianYing,
Yuan Li,
Zheng Jian,
Huang Huilin,
Chen SiQi,
Xiao ZhiWen,
Wang HongBo,
Roy Gaurab,
Zhong Qian,
Lin Dongxin,
Zeng YiXin,
Wang Jinkai,
Zhao Bo,
Gewurz Benjamin E,
Chen Jianjun,
Zuo Zhixiang,
Zeng MuSheng
Publication year - 2021
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202050128
Subject(s) - lytic cycle , nasopharyngeal carcinoma , rna , epstein–barr virus , biology , viral replication , virology , virus , messenger rna , gene , cancer research , genetics , medicine , radiation therapy
N 6 ‐methyladenosine (m 6 A) modification of mRNA mediates diverse cellular and viral functions. Infection with Epstein–Barr virus (EBV) is causally associated with nasopharyngeal carcinoma (NPC), 10% of gastric carcinoma, and various B‐cell lymphomas, in which the viral latent and lytic phases both play vital roles. Here, we show that EBV transcripts exhibit differential m 6 A modification in human NPC biopsies, patient‐derived xenograft tissues, and cells at different EBV infection stages. m 6 A‐modified EBV transcripts are recognized and destabilized by the YTHDF1 protein, which leads to the m 6 A‐dependent suppression of EBV infection and replication. Mechanistically, YTHDF1 hastens viral RNA decapping and mediates RNA decay by recruiting RNA degradation complexes, including ZAP, DDX17, and DCP2, thereby post‐transcriptionally downregulating the expression of EBV genes. Taken together, our results reveal the critical roles of m 6 A modifications and their reader YTHDF1 in EBV replication. These findings contribute novel targets for the treatment of EBV‐associated cancers.