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 collabor...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.展开更多
基金supported by the National Natural Science Foundation of China(31770946,awarded to Y.Y.)Key Research Programs of Frontier Science(awarded to Y.Y.W.)funded by Chinese Academy of Sciences。
文摘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.
