RNF20 dual regulation of MDA5 signaling to maintain immune homeostasis in chickens

• DOI: 10.1128/jvi.02008-24
• Publication Date: 2025-02-25T13:50:27Z
• Authors: Jie Wang; Qiuju Liu; Kehui Zhang; Shurui Zhao; Qi Shao; Feiyu Fu; Jingjiao Ma; Zhaofei Wang; Ya-xian Yan; Hengan Wang; Jianhe Sun; Yuqiang Cheng
• Keywords: MDA5; RIG-I

ABSTRACT RIG-I and MDA5, known as the RIG-I-like receptors (RLRs), play a pivotal role in inducing antiviral responses to RNA viral infections. While chickens lack RIG-I, they possess functionally enhanced MDA5 that recognizes pathogens regulates immunity, underscoring critical of maintaining immune homeostasis chickens. However, precise mechanisms governing expression optimal activation remain unclear. Here, we reveal chicken E3 ubiquitin ligase RNF20 is essential for modulating MDA5-mediated innate homeostasis. Transcriptome sequencing analysis revealed infection DF-1 cells significantly upregulated RNF20. Overexpression markedly suppresses immunity-related genes, while knockout leads deficiency both vivo vitro . Mechanistically, located nucleus, where it maintains basic inducible establish defense during early phase. In late phase, translocates cytoplasm, facilitates K27- K48-linked polyubiquitination subsequent degradation thereby preventing overstimulation. Overall, this study establishes an important IMPORTANCE Chicken sensor initiating response. The protein level must be tightly regulated maintain study, demonstrate precisely stabilization through nucleoplasmic translocation. Specifically, uninfected infection, transcription nucleus. stages out nucleus catalyzes ubiquitinated MDA5. Thus, regulating