Premium
RNF 123 has an E3 ligase‐independent function in RIG ‐I‐like receptor‐mediated antiviral signaling
Author(s) -
Wang Shuai,
Yang YongKang,
Chen Tao,
Zhang Heng,
Yang WeiWei,
Song ShengSheng,
Zhai ZhongHe,
Chen DanYing
Publication year - 2016
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201541703
Subject(s) - rig i , sendai virus , ubiquitin ligase , microbiology and biotechnology , biology , gene knockdown , signal transducing adaptor protein , signal transduction , innate immune system , receptor , virus , gene , virology , biochemistry , ubiquitin
Retinoic acid‐inducible gene I ( RIG ‐I) and melanoma differentiation‐associated gene 5 ( MDA 5) are cytoplasmic sensors crucial for recognizing different species of viral RNA s, which triggers the production of type I interferons ( IFN s) and inflammatory cytokines. Here, we identify RING finger protein 123 ( RNF 123) as a negative regulator of RIG ‐I and MDA 5. Overexpression of RNF 123 inhibits IFN ‐β production triggered by Sendai virus (SeV) and encephalomyocarditis picornavirus ( EMCV ). Knockdown or knockout of endogenous RNF 123 potentiates IFN ‐β production triggered by SeV and EMCV , but not by the sensor of DNA viruses cGAS . RNF 123 associates with RIG ‐I and MDA 5 in both endogenous and exogenous cases in a viral infection‐inducible manner. The SPRY and coiled‐coil, but not the RING , domains of RNF 123 are required for the inhibitory function. RNF 123 interacts with the N‐terminal CARD domains of RIG ‐I/ MDA 5 and competes with the downstream adaptor VISA / MAVS / IPS ‐1/Cardif for RIG ‐I/ MDA 5 CARD binding. These findings suggest that RNF 123 functions as a novel inhibitor of innate antiviral signaling mediated by RIG ‐I and MDA 5, a function that does not depend on its E3 ligase activity.