Stratified ubiquitination of RIG-I creates robust immune response and induces selective gene expression.

ABSTRACT: The activation of retinoic acid-inducible gene I (RIG-I), an indispensable viral RNA sensor in mammals, is subtly regulated by ubiquitination. Although multiple ubiquitination sites at the amino terminus of RIG-I have been identified, their functional allocations in RIG-I activation remain elusive. We identified a stratified model for RIG-I amino-terminal ubiquitination, in which initiation at either Lys¹⁶⁴ or Lys¹⁷² allows subsequent ubiquitination at other lysines, to trigger and amplify RIG-I activation. Experimental and mathematical modeling showed that multisite ubiquitination provides robustness in RIG-I-mediated type I interferon (IFN) signaling. Furthermore, the flexibly controlled ultrasensitivity and IFN activation intensity determine the specificity of the

SUBMITTER: Xian H 

PROVIDER: S-EPMC5609842 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature