Formation of SUMO3-conjugated chains of MAVS induced by poly(dA:dT), a ligand of RIG-I, enhances the aggregation of MAVS that drives the secretion of interferon-β in human keratinocytes

• Published in: Biochemical and biophysical research communications 2020-02, Vol.522 (4), p.939-944
• Main Authors: Choi, Go Woon, Lee, Yujin, Yun, Mihee, Kang, Junghoon, Lee, Seong-Beom
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Cell Line; DEAD Box Protein 58 - metabolism; Humans; IFN-β; Interferon-beta - metabolism; Keratinocyte; Keratinocytes - drug effects; Keratinocytes - metabolism; Ligands; MAVS; Poly dA-dT - pharmacology; Protein Aggregates - drug effects; Protein Domains; Receptors, Immunologic; RIG-I; RNA, Small Interfering - metabolism; Salicylates - pharmacology; Sequence Deletion; SUMO; Sumoylation - drug effects; Ubiquitin-Conjugating Enzymes - metabolism; Ubiquitins - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2019.11.189

The retinoic-acid inducible gene (RIG)-I is a cytoplasmic pattern recognition receptor that senses single-stranded (ss) or double-stranded (ds) RNA. RIG-I also senses AT-rich dsDNA, poly(dA:dT), through the action of an RNA polymerase III-transcribed RNA intermediate. Upon the binding of an RNA ligand, RIG-I binds to the mitochondrial antiviral-signaling protein (MAVS) and induces the formation of filamentous aggregates of MAVS, leading to the formation of a signaling complex that drives Type I interferon (IFN) responses. In the current study, we investigated the issue of whether the SUMOylation of MAVS induced by poly(dA:dT) affects the aggregation of MAVS in the RIG-I/MAVS pathway in human keratinocytes. Our results show that the poly(dA:dT)-induced secretion of IFN-β was dependent on RIG-I and MAVS. The inhibition of SUMOylation by Ginkgolic acid or Ubc9 siRNA was found to inhibit the poly(dA:dT)-induced secretion of IFN-β, suggesting that the SUMOylation is required for the poly(dA:dT)-activated RIG-I/MAVS pathway, which drives the secretion of IFN-β. In addition, treatment with poly(dA:dT) enhanced the formation of polymeric chains of small-ubiquitin like modifiers (SUMO)3, but not SUMO1 and SUMO2, on MAVS. Our results also show that the conjugation of SUMO3 to MAVS induced by poly (dA:dT) enhanced the aggregation of MAVS. These collective results show that the formation of SUMO3-conjugated chains of MAVS induced by poly (dA:dT), a ligand of RIG-I, enhances the aggregation of MAVS which, in turn, drives the secretion of IFN-β in human keratinocytes. •Poly(dA:dT)-induced secretion of IFN-β is dependent on RIG-I and MAVS in human keratinocytes.•Inhibition of SUMOylation by Ginkgolic acid and Ubc9 siRNA inhibits poly(dA:dT)-induced secretion of IFN-β in human keratinocytes.•Poly(dA:dT) induces the formation of SUMO3-conjugated chains of MAVS in human keratinocytes.•The conjugation of SUMO3 to MAVS induced by poly(dA:dT) enhances the aggregation of MAVS that drives the secretion of IFN-β in human keratinocytes.