SRP54 Negatively Regulates IFN-Beta Production and Antiviral Response by Targeting RIG-I and MDA5

During virus infection, RIG-I-like receptors(RLRs) recognize viral RNAs and recruit the adaptor protein VISA to activate downstream signaling, leading to activation of transcription factors NF-κB and IRF3, which collaborate to induce type I interferons(IFNs). IFNs further induce expression of hundreds of IFN-stimulated genes(ISGs) that suppress viral replication and facilitate the adaptive immune response. Dysregulated production of IFNs is implicated in various immune diseases. Here we identified Signal Recognition Particle 54(SRP54) as a negative regulator of RLRs-induced antiviral signaling. Overexpression of SRP54 inhibited RNA virus-triggered induction of IFN-b and increased viral replication,whereas knockdown of SRP54 had opposite effects. Mechanistically, SRP54 interacted with both RIG-I and MDA5 and impaired their association with VISA. Our findings demonstrate that SRP54 acts as a negative regulator of RLRs-mediated innate immune response by disrupting the recruitment of VISA to RIG-I/MDA5.