Ubiquitination plays a crucial role in retinoic acid-inducible gene I(RIG-I)-induced antiviral responses.However, the precise regulatory mechanisms of RIG-I activity mediated by conjugated and unanchored ubiquitin cha...Ubiquitination plays a crucial role in retinoic acid-inducible gene I(RIG-I)-induced antiviral responses.However, the precise regulatory mechanisms of RIG-I activity mediated by conjugated and unanchored ubiquitin chains remain to be determined. In this study, we discovered that T55 of RIG-I was required for its binding ability for the unanchored ubiquitin chains. Experimental and mathematical analysis showed that unanchored ubiquitin chains associated with RIG-I were essential for sustained activation of type I interferon(IFN) signaling. Transcriptomics study revealed that the binding of RIG-I with unanchored ubiquitin chains additionally regulated the expression of a subset of metabolic and cell fate decision genes. Moreover, we found that ubiquitin-specific peptidase 21(USP21) and USP3 deubiquitinate conjugated and unanchored ubiquitin chains on RIG-I respectively. Taken together, characterization of the regulation mode and functions of conjugated ubiquitination and the unconjugated ubiquitin chainbinding of RIG-I may provide means to fine-tune RIG-I-mediated type I IFN signaling.展开更多
基金supported by the National Key Research and Development Program of China(2020YFA0908700)the National Natural Science Foundation of China(31870862,31700760,31770978,and 91742109)+4 种基金China Postdoctoral Science Foundation(2019M663225)Science and Technology Planning Project of GuangzhouChina(201804010385)Fundamental Research Funds for the Central Universities(18lgpy49)Guangdong Basic and Applied Basic Research Foundation(2019A1515110508)。
文摘Ubiquitination plays a crucial role in retinoic acid-inducible gene I(RIG-I)-induced antiviral responses.However, the precise regulatory mechanisms of RIG-I activity mediated by conjugated and unanchored ubiquitin chains remain to be determined. In this study, we discovered that T55 of RIG-I was required for its binding ability for the unanchored ubiquitin chains. Experimental and mathematical analysis showed that unanchored ubiquitin chains associated with RIG-I were essential for sustained activation of type I interferon(IFN) signaling. Transcriptomics study revealed that the binding of RIG-I with unanchored ubiquitin chains additionally regulated the expression of a subset of metabolic and cell fate decision genes. Moreover, we found that ubiquitin-specific peptidase 21(USP21) and USP3 deubiquitinate conjugated and unanchored ubiquitin chains on RIG-I respectively. Taken together, characterization of the regulation mode and functions of conjugated ubiquitination and the unconjugated ubiquitin chainbinding of RIG-I may provide means to fine-tune RIG-I-mediated type I IFN signaling.
