Critical Role of IRF-3 in the Direct Regulation of dsRNA-Induced Retinoic Acid-Inducible Gene-I (RIG-I) Expression.
Critical Role of IRF-3 in the Direct Regulation of dsRNA-Induced Retinoic Acid-Inducible Gene-I (RIG-I) Expression.
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DOI：
10.1371/journal.pone.0163520
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Imaizumi T
中科院分区：
文献类型：
--
作者：
Hayakari R;Matsumiya T;Xing F;Yoshida H;Hayakari M;Imaizumi T
维甲酸诱导基因-I(RIG-I)，又称干扰素刺激基因(ISG)，是一种细胞质病毒感受器，它通过感应病毒RNA来激活抗病毒信号。因此，人们认为RIG-I是以STAT1依赖的方式调节的。尽管RIG-I介导的抗病毒信号对于诱导适当的适应性免疫反应是必不可少的，但RIG-I表达调控的机制仍然不清楚。在这里，我们研究了干扰素调节因子3(IRF-3)对RIG-I表达的直接调节，IRF-3是抗病毒天然免疫的重要分子。我们初步发现，dsRNA可以通过干扰素依赖和IRF-3依赖的方式诱导RIG-I。序列分析表明，RIG-I基因在其启动子区域具有可能的IRF-3结合位点。利用细胞、分子生物学和突变方法的组合，我们首次证明IRF-3可以通过RIG-I基因近端启动子区域的单个IRF元件(IRF-E)来直接调节RIG-I的表达，以响应dsRNA。IRF-3被认为是I型干扰素(IFN)产生的抗病毒信号的主要调节因子。因此，我们的发现表明，由IRF-3介导的途径诱导的RIG-I的表达可能是通过调节细胞质病毒传感器RIG-I来加强对病毒入侵的监视系统的关键抗病毒因子。
The cytoplasmic viral sensor retinoic acid-inducible gene-I (RIG-I), which is also known as an IFN-stimulated gene (ISG), senses viral RNA to activate antiviral signaling. It is therefore thought that RIG-I is regulated in a STAT1-dependent manner. Although RIG-I-mediated antiviral signaling is indispensable for the induction of an appropriate adaptive immune response, the mechanism underlying the regulation of RIG-I expression remains elusive. Here, we examined the direct regulation of RIG-I expression by interferon regulatory factor 3 (IRF-3), which is an essential molecule for antiviral innate immunity. We initially found that RIG-I can be induced by dsRNA in both IFN-independent and IRF-3-dependent manners. A sequence analysis revealed that the RIG-I gene has putative IRF-3-binding sites in its promoter region. Using a combination of cellular, molecular biological, and mutational approaches, we first showed that IRF-3 can directly regulate the expression of RIG-I via a single IRF-element (IRF-E) site in the proximal promoter region of the RIG-I gene in response to dsRNA. IRF-3 is considered a master regulator in antiviral signaling for the generation of type I interferons (IFNs). Thus, our findings demonstrate that RIG-I expression induced by the IRF-3-mediated pathway may serve as a crucial antiviral factor for reinforcing a surveillance system against viral invasion through the regulation of the cytoplasmic viral sensor RIG-I.
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影响因子：
64.5
作者：
Dixit E;Boulant S;Zhang Y;Lee AS;Odendall C;Shum B;Hacohen N;Chen ZJ;Whelan SP;Fransen M;Nibert ML;Superti-Furga G;Kagan JC
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DOI：
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发表时间：
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5.3
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影响因子：
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作者：
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DOI：
10.1073/pnas.0407639101
发表时间：
2004-12-07
影响因子：
11.1
作者：
Andrejeva, J;Childs, KS;Randall, RE
通讯作者：
Randall, RE