RNA-binding protein RBM47 stabilizes IFNAR1 mRNA to potentiate host antiviral activity
RNA-binding protein RBM47 stabilizes IFNAR1 mRNA to potentiate host antiviral activity
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RNA结合蛋白RBM47稳定IFNAR1 mRNA以增强宿主抗病毒活性
DOI：
10.15252/embr.202052205
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发表时间：
2021-06-23
期刊：
影响因子：
7.7
通讯作者：
Dai, Jianfeng
中科院分区：
文献类型：
--
作者：
Wang, Kezhen;Huang, Chenxiao;Dai, Jianfeng
I型干扰素（IFN-I, ifn - α / β）介导的免疫反应是宿主防御入侵病毒的第一道防线。ifn - α / β结合ifn - α / β受体（IFNARs）并触发ifn刺激基因（isg）的表达。因此，IFNARs的稳定对于延长抗病毒活性非常重要。在这里，我们报道了在病毒感染或干扰素刺激下诱导含有rna结合基序的蛋白RBM47。通过多种病毒感染模型，我们证明RBM47在体内和体外都具有广谱抗病毒活性。RBM47对IFN的产生无明显影响，但可显著激活IFN刺激反应元件（ISRE）并增强干扰素刺激基因（ISGs）的表达。机制上，RBM47结合IFNAR1 mRNA的3'UTR，增加mRNA的稳定性，并延缓IFNAR1的降解。综上所述，本研究提示RBM47是一种干扰素诱导的rna结合蛋白，在增强宿主IFN下游信号传导中发挥重要作用。
The type I interferon (IFN-I, IFN-alpha/beta)-mediated immune response is the first line of host defense against invading viruses. IFN-alpha/beta binds to IFN-alpha/beta receptors (IFNARs) and triggers the expression of IFN-stimulated genes (ISGs). Thus, stabilization of IFNARs is important for prolonging antiviral activity. Here, we report the induction of an RNA-binding motif-containing protein, RBM47, upon viral infection or interferon stimulation. Using multiple virus infection models, we demonstrate that RBM47 has broad-spectrum antiviral activity in vitro and in vivo. RBM47 has no noticeable impact on IFN production, but significantly activates the IFN-stimulated response element (ISRE) and enhances the expression of interferon-stimulated genes (ISGs). Mechanistically, RBM47 binds to the 3'UTR of IFNAR1 mRNA, increases mRNA stability, and retards the degradation of IFNAR1. In summary, this study suggests that RBM47 is an interferon-inducible RNA-binding protein that plays an essential role in enhancing host IFN downstream signaling.