The RNA-binding protein Mex3B is a coreceptor of Toll-like receptor 3 in innate antiviral response.
The RNA-binding protein Mex3B is a coreceptor of Toll-like receptor 3 in innate antiviral response.
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RNA 结合蛋白 Mex3B 是先天抗病毒反应中 Toll 样受体 3 的共同受体
DOI：
10.1038/cr.2016.16
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发表时间：
2016-03
期刊：
影响因子：
44.1
通讯作者：
Wang YY
中科院分区：
文献类型：
--
作者：
Yang Y;Wang SY;Huang ZF;Zou HM;Yan BR;Luo WW;Wang YY
toll样受体3 （TLR3）对病毒dsRNA的识别导致干扰素（ifn）和促炎细胞因子的诱导，以及先天抗病毒反应。在这里，我们通过表达克隆筛选发现rna结合蛋白Mex3B是tlr3介导的信号转导的正调节因子。来自Mex3b - / -小鼠的细胞对dsRNA模拟物poly （I: C）的反应显示IFN-β的产生减少，但与RNA病毒感染无关。注射poly （I: C）的Mex3b - / -小鼠对poly （I: C）诱导的死亡更有抵抗力。在核内体中，Mex3B与TLR3相关。它与dsRNA结合，增加了TLR3的dsRNA结合活性。Mex3B还促进了TLR3的蛋白水解加工，这对其激活至关重要。缺乏其rna结合活性的Mex3B突变体抑制了tlr3介导的IFN-β诱导。这些发现表明，Mex3B在先天抗病毒反应中作为TLR3的辅助受体。
Recognition of viral dsRNA by Toll-like receptor 3 (TLR3) leads to induction of interferons (IFNs) and proinflammatory cytokines, and innate antiviral response. Here we identified the RNA-binding protein Mex3B as a positive regulator of TLR3-mediated signaling by expression cloning screens. Cells from Mex3b−/− mice exhibited reduced production of IFN-β in response to the dsRNA analog poly (I: C) but not infection with RNA viruses. Mex3b−/− mice injected with poly (I: C) was more resistant to poly (I: C)-induced death. Mex3B was associated with TLR3 in the endosomes. It bound to dsRNA and increased the dsRNA-binding activity of TLR3. Mex3B also promoted the proteolytic processing of TLR3, which is critical for its activation. Mutants of Mex3B lacking its RNA-binding activity inhibited TLR3-mediated IFN-β induction. These findings suggest that Mex3B acts as a coreceptor of TLR3 in innate antiviral response.