Cadena, Cristhian, Ahmad, Sadeem, Xavier, Audrey, Willemsen, Joschka, Park, Sehoon, Park, Ji Woo, Oh, Seong-Wook, Fujita, Takashi, Hou, Fajian, Binder, Marco and Hur, Sun (2019) Ubiquitin-Dependent and -Independent Roles of E3 Ligase RIPLET in Innate Immunity. Cell, 177 (5). 1187-1200.e16. ISSN 1097-4172

Abstract

The conventional view posits that E3 ligases function primarily through conjugating ubiquitin (Ub) to their substrate molecules. We report here that RIPLET, an essential E3 ligase in antiviral immunity, promotes the antiviral signaling activity of the viral RNA receptor RIG-I through both Ub-dependent and -independent manners. RIPLET uses its dimeric structure and a bivalent binding mode to preferentially recognize and ubiquitinate RIG-I pre-oligomerized on dsRNA. In addition, RIPLET can cross-bridge RIG-I filaments on longer dsRNAs, inducing aggregate-like RIG-I assemblies. The consequent receptor clustering synergizes with the Ub-dependent mechanism to amplify RIG-I-mediated antiviral signaling in an RNA-length dependent manner. These observations show the unexpected role of an E3 ligase as a co-receptor that directly participates in receptor oligomerization and ligand discrimination. It also highlights a previously unrecognized mechanism by which the innate immune system measures foreign nucleic acid length, a common criterion for self versus non-self nucleic acid discrimination.

Item Type:	Article
Date Deposited:	15 Dec 2020 00:45
Last Modified:	15 Dec 2020 00:45
URI:	https://oak.novartis.com/id/eprint/44031