RNA-binding protein RBM47 stabilizes IFNAR1 mRNA to potentiate host antiviral activity.

Abstract

The type I interferon (IFN-I, IFN-α/β)-mediated immune response is the first line of host defense against invading viruses. IFN-α/β binds to IFN-α/β receptors (IFNARs) and triggers the expression of IFN-stimulated genes (ISGs). Thus, stabilization of IFNARs is important for prolonging antiviral activity. Here, we report the induction of an RNA-binding motif-containing protein, RBM47, upon viral infection or interferon stimulation. Using multiple virus infection models, we demonstrate that RBM47 has broad-spectrum antiviral activity invitro and invivo. RBM47 has no noticeable impact on IFN production, but significantly activates the IFN-stimulated response element (ISRE) and enhances the expression of interferon-stimulated genes (ISGs). Mechanistically, RBM47 binds to the 3'UTR of IFNAR1 mRNA, increases mRNA stability, and retards the degradation of IFNAR1. In summary, this study suggests that RBM47 is an interferon-inducible RNA-binding protein that plays an essential role in enhancing host IFN downstream signaling.