RNF144B 通过靶向 MDA5 进行自噬降解来负向调节抗病毒免疫。

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2024-09-16 DOI:10.1038/s44319-024-00256-w

Guoxiu Li,Jing Zhang,Zhixun Zhao,Jian Wang,Jiaoyang Li,Weihong Xu,Zhanding Cui,Pu Sun,Hong Yuan,Tao Wang,Kun Li,Xingwen Bai,Xueqing Ma,Pinghua Li,Yuanfang Fu,Yimei Cao,Huifang Bao,Dong Li,Zaixin Liu,Ning Zhu,Lijie Tang,Zengjun Lu

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引用次数: 0

摘要

作为一种类似 RIG-I 的受体，MDA5 在抗病毒先天免疫中发挥着关键作用，它是一种细胞质双链 RNA 传感器，能够启动 I 型干扰素通路。在这里，我们发现 RNF144B 与 MDA5 有特异性相互作用，并促进 MDA5 在赖氨酸 23 和赖氨酸 43 上的 K27/K33 链接多泛素化，从而促进 p62 对 MDA5 的自噬降解。缺乏 Rnf144b 会大大促进 IFN 的产生并抑制 EMCV 在体内的复制。重要的是，Rnf144b-/-小鼠感染EMCV后的总存活率明显高于野生型小鼠。总之，我们的研究结果表明，RNF144B 通过靶向 MDA5 的 CARDs 和介导 MDA5 的自噬降解，是先天性抗病毒反应的负调控因子。

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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-/- 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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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

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