Cells can sense invading viruses and trigger type I interferons (IFN-α/β) to evoke antiviral innate immune response. Induction of IFNs needs to be fine-tuned to achieve the antiviral consequence while avoiding severe disruption of host cell homeostasis. Here, we reported that NAT10, the acetyltransferase of histone and N4-acetylcytidine (ac4C) RNA modification, promotes infection of RNA viruses via regulation of type I IFN signaling. Depletion of NAT10 increased the expression of IFN-β and interferon-stimulated genes (ISGs) upon stimulation of type I IFN antiviral signaling, while it impaired viral replication. NAT10 dynamically associated with the IFN-β promotor and negatively regulated IRF3 through modulation of long non-coding RNAs (lncRNAs) that inhibit IRFs. Consistently, the small molecule inhibitor of NAT10, Remodelin, increased IFN-β expression while inhibiting viral infections. Overall, our findings indicated that NAT10 is a negative regulator of type I IFN signaling, suggesting its potential as a target of antiviral treatment.
Keywords: IRF3; NAT10; antiviral; immune signaling; interferon; remodelin; virus.