The protein arginine methyltransferase PRMT1 promotes TBK1 activation through asymmetric arginine methylation

TBK1 is an essential kinase for the innate immune response against viral infection. However, the key molecular mechanisms regulating the TBK1 activation remain elusive. Here, we identify PRMT1, a type I protein arginine methyltransferase, as an essential regulator of TBK1 activation. PRMT1 directly interacts with TBK1 and catalyzes asymmetric methylation of R54, R134, and R228 on TBK1. This modification enhances TBK1 oligomerization after viral infection, which subsequently promotes TBK1 phosphorylation and downstream type I interferon production. More important, myeloid-specific Prmt1 knockout mice are more susceptible to infection with DNA and RNA viruses than Prmt1fl/fl mice. Our findings reveal insights into the molecular regulation of TBK1 activation and demonstrate the essential function of protein arginine methylation in innate antiviral immunity. [Display omitted] •PRMT1 positively regulates IFN-β signaling in various innate immune signaling pathways•Prmt1 knockout mice are more susceptible to viral infection than their counterparts•PRMT1 promotes antiviral responses through catalyzing the methylation of TBK1•TBK1 methylation is essential for its aggregation and trans-autophosphorylation Yan et al. find that PRMT1 positively regulates antiviral innate immune responses in a methyltransferase-dependent manner. PRMT1 catalyzes asymmetric methylation of R54, R134, and R228 on TBK1 upon viral infection and promotes TBK1 aggregation and phosphorylation. These findings demonstrate the essential function of PRMT1 for antiviral immunity.