A finTRIM Family Protein Acquires RNA-Binding Activity and E3 Ligase Activity to Shape the IFN Response in Fish

In this study, we identify FTRCA1 as an RNA-binding E3 ligase and characterize the contribution of its RNA-binding activity and E3 ligase activity to fish IFN response. Besides targeting TBK1 and IRF7, FTRCA1 downregulates fish IFN response also by targeting stimulator of IFN response cGAMP interactor 1 (STING1). E3 ligase activity is required for full inhibition on the TBK1- and IRF7-mediated IFN response, but partial inhibition on the STING1-mediated IFN response. However, FTRCA1 has a general binding potential to mRNAs in vitro, it selectively binds STING1 and IRF7 mRNAs in vivo to attenuate mRNA levels, and it directly interacts with TBK1 protein to target protein degradation for downregulating the IFN response. Our results present an interesting example of a fish species-specific finTRIM protein that has acquired RNA-binding activity and E3 ligase activity to fine-tune fish IFN response.PMID:36165180 | DOI:10.4049/jimmunol.2200343
Source: Journal of Immunology - Category: Allergy & Immunology Authors: Source Type: research