Arginine Monomethylation by PRMT7 Controls MAVS-Mediated Antiviral Innate Immunity

Abstract

Accurate control of innate immune responses is required to eliminate invading pathogens and simultaneously avoid autoinflammation and autoimmune diseases. Here, we demonstrate that the arginine monomethylation, a relative barely studied protein modification in innate immunity, precisely regulates mitochondrial antiviral-signaling protein (MAVS)-mediated antiviral response. PRMT7 forms aggregates to catalyze MAVS monomethylation at arginine residue 52 (R52), attenuating its binding to TRIM31 and RIG-I, which leads to the suppression of MAVS aggregation, and subsequent activation. Upon virus infection, aggregated PRMT7 is disabled timely due to automethylated at arginine residue 32 (R32), and SMURF1 is recruited to PRMT7 by MAVS to induce proteasomal degradation of PRMT7, resulting in the relief of PRMT7 suppression on MAVS activation. PRMT7 inhibitor SGC3027 can protect mice from virus infection by blocking enzymatic activity of PRMT7. Therefore, we not only reveal that arginine monomethylation by PRMT7 negatively regulates MAVS-mediated antiviral signaling in vitro and in vivo, but also uncover a mechanism by which PRMT7 is tightly controlled to ensure timely activation of antiviral defense.