DDX60, a DEXD/H Box Helicase, Is a Novel Antiviral Factor Promoting RIG-I-Like Receptor-Mediated Signaling
DDX60, a DEXD/H Box Helicase, Is a Novel Antiviral Factor Promoting RIG-I-Like Receptor-Mediated Signaling
复制标题
DOI：
10.1128/mcb.01368-10
复制
发表时间：
2011-09-01
影响因子：
5.3
通讯作者：
Seya, Tsukasa
中科院分区：
文献类型：
--
作者：
Miyashita, Moeko;Oshiumi, Hiroyuki;Seya, Tsukasa
细胞质病毒 RNA 传感器 RIG-I 和 MDA5 对于 I 型干扰素和其他炎症细胞因子的产生很重要。 DDX60 是一种未表征的 DEXD/H 盒 RNA 解旋酶，类似于酿酒酵母 Ski2，后者是 RNA 外泌体的辅助因子，而 RNA 外泌体是细胞质 RNA 完整性所需的蛋白质复合物。病毒感染后DDX60表达增加，并且该蛋白定位于细胞质区域。病毒感染后，DDX60 蛋白与内源性 RIG-I 蛋白结合。该蛋白还与 MDA5 和 LGP2 结合，但不与下游因子 IPS-1 和 I kappa B 激酶 epsilon (IKK-epsilon) 结合。敲低分析表明，RIG-I 或 MDA5 依赖性 I 型干扰素和响应病毒感染的干扰素诱导基因表达需要 DDX60。然而，DDX60 对于 TLR3 介导的信号传导来说是可有可无的。纯化的 DDX60 解旋酶结构域具有结合病毒 RNA 和 DNA 的活性。 DDX60 的表达促进 RIG-I 与双链 RNA 的结合。综上所述，我们的分析表明 DDX60 是一种新型抗病毒解旋酶，可促进 RIG-I 样受体介导的信号传导。
The cytoplasmic viral RNA sensors RIG-I and MDA5 are important for the production of type I interferon and other inflammatory cytokines. DDX60 is an uncharacterized DEXD/H box RNA helicase similar to Saccharomyces cerevisiae Ski2, a cofactor of RNA exosome, which is a protein complex required for the integrity of cytoplasmic RNA. Expression of DDX60 increases after viral infection, and the protein localizes at the cytoplasmic region. After viral infection, the DDX60 protein binds to endogenous RIG-I protein. The protein also binds to MDA5 and LGP2 but not to the downstream factors IPS-1 and I kappa B kinase epsilon (IKK-epsilon). Knockdown analysis shows that DDX60 is required for RIG-I-or MDA5-dependent type I interferon and interferon-inducible gene expression in response to viral infection. However, DDX60 is dispensable for TLR3-mediated signaling. Purified DDX60 helicase domains possess the activity to bind to viral RNA and DNA. Expression of DDX60 promotes the binding of RIG-I to double-stranded RNA. Taken together, our analyses indicate that DDX60 is a novel antiviral helicase promoting RIG-I-like receptor-mediated signaling.