2. Academic Validation
  3. METTL3 regulates viral m6A RNA modification and host cell innate immune responses during SARS-CoV-2 infection

METTL3 regulates viral m6A RNA modification and host cell innate immune responses during SARS-CoV-2 infection

  • Cell Rep. 2021 May 11;35(6):109091. doi: 10.1016/j.celrep.2021.109091.
Na Li 1,  Hui Hui 2,  Bill Bray 1,  Gwendolyn Michelle Gonzalez 3,  Mark Zeller 4,  Kristian G Anderson 4,  Rob Knight 5,  Davey Smith 6,  Yinsheng Wang 3,  Aaron F Carlin 6,  Tariq M Rana 7
Affiliations

Affiliations

  • 1 Division of Genetics, Program in Immunology, Institute for Genomic Medicine, University of California, San Diego, 9500 Gilman Drive MC 0762, La Jolla, CA 92093, USA; Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive MC 0762, La Jolla, CA 92093, USA.
  • 2 Division of Genetics, Program in Immunology, Institute for Genomic Medicine, University of California, San Diego, 9500 Gilman Drive MC 0762, La Jolla, CA 92093, USA; Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive MC 0762, La Jolla, CA 92093, USA; Bioinformatics Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
  • 3 Environmental Toxicology Graduate Program and Department of Chemistry, University of California, Riverside, Riverside, CA 92521, USA.
  • 4 Department of Immunology and Microbiology, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
  • 5 Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive MC 0762, La Jolla, CA 92093, USA; Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Center for Microbiome Innovations, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
  • 6 Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
  • 7 Division of Genetics, Program in Immunology, Institute for Genomic Medicine, University of California, San Diego, 9500 Gilman Drive MC 0762, La Jolla, CA 92093, USA; Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive MC 0762, La Jolla, CA 92093, USA. Electronic address: [email protected].
PMID: 33961823 DOI: 10.1016/j.celrep.2021.109091
Abstract

It is urgent and important to understand the relationship of the widespread severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) with host immune response and study the underlining molecular mechanism. N6-methylation of adenosine (m6A) in RNA regulates many physiological and disease processes. Here, we investigate m6A modification of the SARS-CoV-2 gene in regulating the host cell innate immune response. Our data show that the SARS-CoV-2 virus has m6A modifications that are enriched in the 3' end of the viral genome. We find that depletion of the host cell m6A methyltransferase METTL3 decreases m6A levels in SARS-CoV-2 and host genes, and m6A reduction in viral RNA increases RIG-I binding and subsequently enhances the downstream innate immune signaling pathway and inflammatory gene expression. METTL3 expression is reduced and inflammatory genes are induced in patients with severe coronavirus disease 2019 (COVID-19). These findings will aid in the understanding of COVID-19 pathogenesis and the design of future studies regulating innate immunity for COVID-19 treatment.

Keywords

METTL3; RIG-I; SARS-CoV-2; host innate immunity; inflammation; m(6)A RNA modification.

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