State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.
PLoS Pathog. 2020 Feb 6;16(2):e1008293. doi: 10.1371/journal.ppat.1008293. eCollection 2020 Feb.
RIG-I plays important roles in pathogen sensing and activation of antiviral innate immune responses in response to RNA viruses. RIG-I-mediated signaling must be precisely controlled to maintain innate immune signaling homeostasis. Previous studies demonstrated that lysine 63 (K63)-linked polyubiquitination of RIG-I is vital for its activation, but the mechanisms through which RIG-I is deubiquitinated to control innate immune responses are not well understood. Here we identified USP27X as a negative regulator of antiviral signaling in response to RNA viruses through siRNA library screening. Further functional studies indicated that USP27X negatively modulated RIG-I-mediated antiviral signaling in a deubiquitinase-dependent manner. Mechanistically, we found that USP27X removed K63-linked polyubiquitin chains from RIG-I to negatively modulate type I interferon signaling. Collectively, these studies uncover a novel negative regulatory role of USP27X in targeting RIG-I to balance innate immune responses.
RIG-I 在病原体感应和激活抗病毒先天免疫反应方面发挥着重要作用，可响应 RNA 病毒。RIG-I 介导的信号必须被精确控制，以维持先天免疫信号的平衡。先前的研究表明，RIG-I 的赖氨酸 63（K63）连接多泛素化对其激活至关重要，但控制先天免疫反应的 RIG-I 去泛素化的机制尚不清楚。在这里，我们通过 siRNA 文库筛选鉴定出 USP27X 是一种负调控 RNA 病毒抗病毒信号的蛋白。进一步的功能研究表明，USP27X 以去泛素酶依赖的方式负调控 RIG-I 介导的抗病毒信号。在机制上，我们发现 USP27X 从 RIG-I 上去除 K63 连接的多泛素链，从而负调控 I 型干扰素信号。总的来说，这些研究揭示了 USP27X 在靶向 RIG-I 以平衡先天免疫反应方面的新的负调控作用。
