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Significance Understanding the molecular mechanisms of SARS-CoV-2 viral pathogenesis and developing novel inhibitors are essential and urgent. Using genome-wide N6,2′-O-dimethyladenosine (m6Am)-exo-seq, RNA-seq analysis, and CRISPR/Cas9 genome editing, we discovered that… Click to show full abstract
Significance Understanding the molecular mechanisms of SARS-CoV-2 viral pathogenesis and developing novel inhibitors are essential and urgent. Using genome-wide N6,2′-O-dimethyladenosine (m6Am)-exo-seq, RNA-seq analysis, and CRISPR/Cas9 genome editing, we discovered that phosphorylated CTD-interacting factor 1 (PCIF1), a cap-specific adenine N6-methyltransferase, plays a major role in facilitating infection of primary human lung epithelial cells and cell lines by SARS-CoV-2, variants of concern, and other coronaviruses. PCIF1 promotes infection by sustaining expression of the coronavirus receptors ACE2 and TMPRSS2 via m6Am-dependent mRNA stabilization. These results suggest a role for PCIF1 and cap m6Am in regulating SARS-CoV-2 susceptibility and identify a potential therapeutic target for prevention of infection.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2023
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