Altered m6A Modification of Specific Cellular Transcripts Affects Flaviviridae Infection
Altered m6A Modification of Specific Cellular Transcripts Affects Flaviviridae Infection
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DOI：
10.1016/j.molcel.2019.11.007
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发表时间：
2020-02-06
期刊：
影响因子：
16
通讯作者：
Horner, Stacy M.
中科院分区：
文献类型：
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作者：
Gokhale, Nandan S.;McIntyre, Alexa B. R.;Horner, Stacy M.
RNA修饰的N-6-甲基腺苷(m(6)A)调节mRNA的命运，从而影响许多生物过程。我们分析了登革病毒(DENV)、寨卡病毒(ZIKV)、西尼罗河病毒(WNV)和丙型肝炎病毒(HCV)感染后m(6)A的转录组。我们发现，感染黄病毒家族中的这些病毒会改变特定细胞转录产物的修饰，包括RIOK3和CIRBP。在病毒感染期间，将m(6)A添加到RIOK3可促进其翻译，而在CIRBP中m(6)A的缺失可促进选择性剪接。重要的是，病毒激活的先天免疫感知或内质网(ER)应激反应分别导致了RIOK3或CIRBP中m(6)A的变化。此外，几个感染改变m(6)A谱的转录本，包括RIOK3和CIRBP，编码影响DENV、ZIKV和丙型肝炎病毒感染的蛋白质。总体而言，这项工作揭示了在病毒感染期间激活的细胞信号通路导致m(6)宿主mRNAs的改变以调节感染。
The RNA modification N-6-methyladenosine (m(6)A) modulates mRNA fate and thus affects many biological processes. We analyzed m(6)A 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 m(6)A modification of specific cellular transcripts, including RIOK3 and CIRBP. During viral infection, the addition of m(6)A to RIOK3 promotes its translation, while loss of m(6)A in CIRBP promotes alternative splicing. Importantly, viral activation of innate immune sensing or the endoplasmic reticulum (ER) stress response contributes to the changes in m(6)A in RIOK3 or CIRBP, respectively. Further, several transcripts with infection-altered m(6)A 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 m(6)A modification of host mRNAs to regulate infection.