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A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
Unanchored ubiquitin chain sustains RIG-I-induced interferon-I activation and controls selective gene expression
Huifang Xian1, Wanming Huang2, Tingzhe Sun3
1MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; Department of Gastroenterology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China.
Abstract:
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 chain-binding of RIG-I may provide means to fine-tune RIG-I-mediated type I IFN signaling.
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