The RNA modification N6-methyladenosine (m6A) modulates mRNA fate and thus affects many biological processes. We analyzed m6A across the transcriptome following infection by dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), and hepatitis C virus (HCV). We found that infection by these viruses in the Flaviviridae family alters m6A modification of specific cellular transcripts, including RIOK3 and CIRBP. During viral infection, the addition of m6A to RIOK3 promotes its translation, while loss of m6A in CIRBP promotes alternative splicing. Importantly, viral activation of innate immune sensing or the endoplasmic reticulum (ER) stress response contributes to the changes in m6A in RIOK3 or CIRBP, respectively. Further, several transcripts with infection-altered m6A profiles, including RIOK3 and CIRBP, encode proteins that influence DENV, ZIKV, and HCV infection. Overall, this work reveals that cellular signaling pathways activated during viral infection lead to alterations in m6A modification of host mRNAs to regulate infection.

中文翻译：

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特定细胞转录物的 m6A 修饰改变影响黄病毒科感染。

RNA 修饰 N6-甲基腺苷 (m6A) 调节 mRNA 的命运，从而影响许多生物过程。我们分析了登革热病毒 (DENV)、寨卡病毒 (ZIKV)、西尼罗河病毒 (WNV) 和丙型肝炎病毒 (HCV) 感染后转录组中的 m6A。我们发现黄病毒科中这些病毒的感染改变了特定细胞转录物的 m6A 修饰，包括 RIOK3 和 CIRBP。在病毒感染期间，向 RIOK3 添加 m6A 促进了其翻译，而 CIRBP 中 m6A 的缺失促进了选择性剪接。重要的是，先天免疫传感或内质网 (ER) 应激反应的病毒激活分别导致 RIOK3 或 CIRBP 中 m6A 的变化。此外，包括 RIOK3 和 CIRBP 在内的几种具有感染改变的 m6A 谱的转录本编码了影响 DENV 的蛋白质，ZIKV 和 HCV 感染。总体而言，这项工作揭示了病毒感染期间激活的细胞信号通路导致宿主 mRNA 的 m6A 修饰的改变，以调节感染。