AI Article Synopsis
- MDA5 is a key receptor that helps the body's immune system detect and respond to viral infections by sensing double-stranded RNA and triggering type I interferon production.
- RNF144B interacts with MDA5, adding specific ubiquitin chains to it, which leads to MDA5's removal through autophagy—a cellular cleanup process.
- Mice lacking RNF144B show increased production of interferon and reduced viral replication, resulting in better survival rates against EMCV infections compared to normal mice, highlighting RNF144B's role as a negative regulator of antiviral responses.
Article Abstract
As a RIG-I-like receptor, MDA5 plays a critical role in antiviral innate immunity by acting as a cytoplasmic double-stranded RNA sensor capable of initiating type I interferon pathways. Here, we show that RNF144B specifically interacts with MDA5 and promotes K27/K33-linked polyubiquitination of MDA5 at lysine 23 and lysine 43, which promotes autophagic degradation of MDA5 by p62. Rnf144b deficiency greatly promotes IFN production and inhibits EMCV replication in vivo. Importantly, Rnf144b mice has a significantly higher overall survival rate than wild-type mice upon EMCV infection. Collectively, our results identify RNF144B as a negative regulator of innate antiviral response by targeting CARDs of MDA5 and mediating autophagic degradation of MDA5.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467429 | PMC |
| http://dx.doi.org/10.1038/s44319-024-00256-w | DOI Listing |
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