A DNA-sensing-independent role of a nuclear RNA helicase, DHX9, in stimulation of NF-κB-mediated innate immunity against DNA virus infection.
A DNA-sensing-independent role of a nuclear RNA helicase, DHX9, in stimulation of NF-κB-mediated innate immunity against DNA virus infection.
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DOI：
10.1093/nar/gky742
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发表时间：
2018-09-28
影响因子：
14.9
通讯作者：
Song MJ
中科院分区：
文献类型：
--
作者：
Ng YC;Chung WC;Kang HR;Cho HJ;Park EB;Kang SJ;Song MJ
DExD/H-box 解旋酶 9 (DHX9) 或 RNA 解旋酶 A (RHA) 是一种丰富的多功能核蛋白。尽管之前有报道称 DHX9 在浆细胞样树突状细胞 (pDC) 中充当胞质 DNA 传感器，但在 DNA 病毒感染期间 DHX9 在非 pDC 细胞中的作用和分子作用机制尚不清楚。在这里，DHX9 的巨噬细胞特异性敲除和成纤维细胞特异性敲除损害了针对 DNA 病毒的抗病毒先天免疫，导致病毒复制增加。 DHX9 增强了细胞核中 NF-κB 介导的反式激活，这需要其 ATP 酶依赖性解旋酶（ATPase/解旋酶）结构域，但不需要胞质 DNA 传感结构域。此外，DNA病毒感染不会诱导巨噬细胞和成纤维细胞中核DHX9的细胞质易位。核 DHX9 与包含 NF-κB p65 和含有 NF-κB 结合位点的染色质中的 RNA 聚合酶 II (RNAPII) 的多蛋白复合物相关。 DHX9 对于将 RNAPII 而不是 NF-κB p65 招募到相应的启动子至关重要；该功能还需要其 ATP 酶/解旋酶活性。综上所述，我们的结果表明核 DHX9（作为转录共激活剂）在刺激 NF-κB 介导的针对 DNA 病毒感染的先天免疫中发挥着关键作用，独立于 DHX9 的 DNA 传感功能。
DExD/H-box helicase 9 (DHX9), or RNA helicase A (RHA), is an abundant multifunctional nuclear protein. Although it was previously reported to act as a cytosolic DNA sensor in plasmacytoid dendritic cells (pDCs), the role and molecular mechanisms of action of DHX9 in cells that are not pDCs during DNA virus infection are not clear. Here, a macrophage-specific knockout and a fibroblast-specific knockdown of DHX9 impaired antiviral innate immunity against DNA viruses, leading to increased virus replication. DHX9 enhanced NF-κB–mediated transactivation in the nucleus, which required its ATPase-dependent helicase (ATPase/helicase) domain, but not the cytosolic DNA-sensing domain. In addition, DNA virus infection did not induce cytoplasmic translocation of nuclear DHX9 in macrophages and fibroblasts. Nuclear DHX9 was associated with a multiprotein complex including both NF-κB p65 and RNA polymerase II (RNAPII) in chromatin containing NF-κB–binding sites. DHX9 was essential for the recruitment of RNAPII rather than NF-κB p65, to the corresponding promoters; this function also required its ATPase/helicase activity. Taken together, our results show a critical role of nuclear DHX9 (as a transcription coactivator) in the stimulation of NF-κB–mediated innate immunity against DNA virus infection, independently of DHX9’s DNA-sensing function.
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影响因子：
3.7
作者：
Liu, Zhe;Kenworthy, Rachael;Tang, Hengli
通讯作者：
Tang, Hengli
影响因子：
6
作者：
Ng, Yee Ching;Kim, Ye Won;Song, Moon Jung
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Song, Moon Jung
影响因子：
4.5
作者：
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通讯作者：
Grinde B
DOI：
10.1083/jcb.152.1.75
发表时间：
2001-01-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Pellizzoni L;Charroux B;Rappsilber J;Mann M;Dreyfuss G
通讯作者：
Dreyfuss G
影响因子：
24.1
作者：
通讯作者：
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