RIG-I is a pivotal cytoplasmic sensor that recognizes different species of viral RNAs. This recognition leads to activation of the transcription factors NF-κB and IRF3, which collaborate to induce type I interferons ...RIG-I is a pivotal cytoplasmic sensor that recognizes different species of viral RNAs. This recognition leads to activation of the transcription factors NF-κB and IRF3, which collaborate to induce type I interferons （IFNs） and innate antiviral response. In this study, we identified the TRIM family protein TRIM4 as a positive regulator of RIG-I-mediated IFN induction. Overexpression of TRIM4 potentiated virus-triggered activation of IRF3 and NF-κB, as well as IFN-13 induction, whereas knockdown of TRIM4 had opposite effects. Mechanistically, TRIM4 associates with RIG-I and targets it for K63-linked poiyubiquitination. Our findings demonstrate that TRIM4 is an important regulator of the virus-induced IFN induction pathways by mediating RIG-I for K63-Unked ubiquitination.展开更多
基金Funding This work was supported by grants from the Ministry of Science and Technology of China （2012CB910201 and 2010CB911802） and the National Natural Science Foundation of China （31221061, 31130020, and 91029302）.
文摘RIG-I is a pivotal cytoplasmic sensor that recognizes different species of viral RNAs. This recognition leads to activation of the transcription factors NF-κB and IRF3, which collaborate to induce type I interferons （IFNs） and innate antiviral response. In this study, we identified the TRIM family protein TRIM4 as a positive regulator of RIG-I-mediated IFN induction. Overexpression of TRIM4 potentiated virus-triggered activation of IRF3 and NF-κB, as well as IFN-13 induction, whereas knockdown of TRIM4 had opposite effects. Mechanistically, TRIM4 associates with RIG-I and targets it for K63-linked poiyubiquitination. Our findings demonstrate that TRIM4 is an important regulator of the virus-induced IFN induction pathways by mediating RIG-I for K63-Unked ubiquitination.
