RNF144B negatively regulates antiviral immunity by targeting MDA5 for autophagic degradation
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<sup>-/-</sup> 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.
Authors
- Guo-Xiu Li (ORCID: https://orcid.org/0000-0003-0831-0516)
- Zhanding Cui (ORCID: https://orcid.org/0000-0002-0661-3954)
- Xingwen Bai
- Yuanfang Fu
- Jiaoyang Li
- Yimei Cao (ORCID: https://orcid.org/0009-0000-1267-9741)
- Zengjun Lu (ORCID: https://orcid.org/0000-0001-9138-692X)
- Lijie Tang (ORCID: https://orcid.org/0000-0002-2423-0076)
- Zhixun Zhao (ORCID: https://orcid.org/0000-0001-5544-4504)
- Zaixin Liu (ORCID: https://orcid.org/0009-0008-9987-386X)
- Pinghua Li (ORCID: https://orcid.org/0000-0003-4314-7400)
- Xueqing Ma (ORCID: https://orcid.org/0009-0003-6780-0061)
- Jian Wang (ORCID: https://orcid.org/0000-0002-5335-8845)
- Kun Li (ORCID: https://orcid.org/0000-0001-8307-634X)
- Dong Li (ORCID: https://orcid.org/0000-0002-8581-8658)
- Tao Wang (ORCID: https://orcid.org/0000-0002-0834-4372)
- Hong Yuan (ORCID: https://orcid.org/0000-0001-9685-2440)
- Weihong Xu
- Ning Zhu
- Jing Zhang (ORCID: https://orcid.org/0000-0002-4965-7076)
- Pu Sun (ORCID: https://orcid.org/0009-0008-2409-401X)
- Huifang Bao
Institutions
- Northeast Agricultural University (CN)
- Lanzhou Veterinary Research Institute (CN)
- Chinese Academy of Agricultural Sciences (CN)
- Gansu Provincial Center for Disease Control and Prevention (CN)
- Lanzhou University (CN)
Publication Details
- Journal
- EMBO Reports
- Published
- 2024-09-16
- DOI
- https://doi.org/10.1038/s44319-024-00256-w
- Citations
- 12
- Primary Topic
- interferon and immune responses
- Type
- article
- Field-Weighted Citation Impact
- 2.89
Funders
- Wenzhou Medical University
- National Natural Science Foundation of China
- Chinese Academy of Agricultural Sciences
- National Key Research and Development Program of China
- Agricultural Science and Technology Innovation Program