Pivotal role of RNA-binding E3 ubiquitin ligase MEX3C in RIG-I–mediated antiviral innate immunity

Significance Upon virus infection, host cells detect viral nucleic acids and induce antiviral innate immune responses by producing cytokines. The retinoic acid inducible gene-1 (RIG-I)-like receptors are cytoplasmic sensors for RNA viruses that mediate antiviral innate immunity. In this study, we identify K homology (KH) domain- and really interesting new gene (RING)-finger domain-containing MEX3C as a molecule that regulates RIG-I function. MEX3C preferentially colocalizes with viral RNA and RIG-I in cytoplasmic granules in infected cells and mediates K63-linked ubiquitination of RIG-I, which is important for activation of downstream signaling. We show that MEX3C is required for cytokine production after infection with RNA viruses that are detected by RIG-I by generating MEXC-deficient mice. Our study demonstrates a critical role of MEX3C in induction of RIGI-mediated antiviral innate immune responses.