Altered m 6 A Modification of Specific Cellular Transcripts Affects Flaviviridae Infection.

Autor:	Gokhale NS; Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27705, USA., McIntyre ABR; Department of Physiology and Biophysics and the Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10065, USA; Tri-Institutional Program in Computational Biology and Medicine, New York, NY 10065, USA., Mattocks MD; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Holley CL; Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27705, USA; Department of Medicine, Duke University Medical Center, Durham, NC 27705, USA., Lazear HM; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Mason CE; Department of Physiology and Biophysics and the Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10065, USA; The HRH Prince Alwaleed Bin Talal Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10065, USA; The WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY 10065, USA; The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10065, USA. Electronic address: chm2042@med.cornell.edu., Horner SM; Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27705, USA; Department of Medicine, Duke University Medical Center, Durham, NC 27705, USA. Electronic address: stacy.horner@duke.edu.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2020 Feb 06; Vol. 77 (3), pp. 542-555.e8. Date of Electronic Publication: 2019 Dec 03.
DOI:	10.1016/j.molcel.2019.11.007
Abstrakt:	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. Competing Interests: Declaration of Interests C.E.M. is a cofounder and board member for Biotia and Onegevity Health and an advisor or compensated speaker for Abbvie, Acuamark Diagnostics, ArcBio, Bio-Rad, DNA Genotek, Genialis, Genpro, Illumina, NEB, QIAGEN, Whole Biome, and Zymo Research. (Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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