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EMBO Rep. 2016 Aug;17(8):1155-68. doi: 10.15252/embr.201541703. Epub 2016 Jun 16.

RNF123 has an E3 ligase-independent function in RIG-I-like receptor-mediated antiviral signaling.

Author information

1
Key Laboratory of Cell Proliferation and Differentiation of The Ministry of Education, School of Life Sciences, Peking University, Beijing, China.
2
Key Laboratory of Cell Proliferation and Differentiation of The Ministry of Education, School of Life Sciences, Peking University, Beijing, China dychen@pku.edu.cn.

Abstract

Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are cytoplasmic sensors crucial for recognizing different species of viral RNAs, which triggers the production of type I interferons (IFNs) and inflammatory cytokines. Here, we identify RING finger protein 123 (RNF123) as a negative regulator of RIG-I and MDA5. Overexpression of RNF123 inhibits IFN-β production triggered by Sendai virus (SeV) and encephalomyocarditis picornavirus (EMCV). Knockdown or knockout of endogenous RNF123 potentiates IFN-β production triggered by SeV and EMCV, but not by the sensor of DNA viruses cGAS RNF123 associates with RIG-I and MDA5 in both endogenous and exogenous cases in a viral infection-inducible manner. The SPRY and coiled-coil, but not the RING, domains of RNF123 are required for the inhibitory function. RNF123 interacts with the N-terminal CARD domains of RIG-I/MDA5 and competes with the downstream adaptor VISA/MAVS/IPS-1/Cardif for RIG-I/MDA5 CARD binding. These findings suggest that RNF123 functions as a novel inhibitor of innate antiviral signaling mediated by RIG-I and MDA5, a function that does not depend on its E3 ligase activity.

KEYWORDS:

IFN‐β; MDA5; RIG‐I; RNF123; innate immunity

PMID:
27312109
PMCID:
PMC4967948
DOI:
10.15252/embr.201541703
[Indexed for MEDLINE]
Free PMC Article

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