TY - JOUR T1 - Altered m<sup>6</sup>A modification of specific cellular transcripts affects <em>Flaviviridae</em> infection JF - bioRxiv DO - 10.1101/670984 SP - 670984 AU - Nandan S. Gokhale AU - Alexa B.R. McIntyre AU - Melissa D. Mattocks AU - Christopher L. Holley AU - Helen M. Lazear AU - Christopher E. Mason AU - Stacy M. Horner Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/06/13/670984.abstract N2 - The RNA modification N6-methyladenosine (m6A) can modulate mRNA fate and thus affect many biological processes. We analyzed m6A modification 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, we found that activation of innate immune sensing or the endoplasmic reticulum (ER) stress response by viral infection contributes to the changes in m6A modification in RIOK3 and 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. ER -