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  • 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 reports (2021-05-08)
Na Li, Hui Hui, Bill Bray, Gwendolyn Michelle Gonzalez, Mark Zeller, Kristian G Anderson, Rob Knight, Davey Smith, Yinsheng Wang, Aaron F Carlin, Tariq M Rana
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-RIG-I, clone 1C3 Antibody, clone 1C3, from mouse
Roche
Biotin RNA Labeling Mix, sufficient for 20 reactions (transcription), pkg of 40 μL, solution