RNA-induced liquid phase separation of SARS-CoV-2 nucleocapsid protein facilitates NF-κB hyper-activation and inflammation.
RNA-induced liquid phase separation of SARS-CoV-2 nucleocapsid protein facilitates NF-κB hyper-activation and inflammation.
复制标题
RNA 诱导的 SARS-CoV-2 核衣壳蛋白液相分离促进 NF-κB 过度激活和炎症
DOI：
10.1038/s41392-021-00575-7
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发表时间：
2021-04-24
影响因子：
39.3
通讯作者：
Cui J
中科院分区：
文献类型：
--
作者：
Wu Y;Ma L;Cai S;Zhuang Z;Zhao Z;Jin S;Xie W;Zhou L;Zhang L;Zhao J;Cui J
由SARS-CoV-2引起的2019年新型冠状病毒病（COVID-19）正在全球范围内流行，并构成重大的全球公共卫生威胁。COVID-19的严重程度和死亡率与病毒诱导的功能失调性炎症反应和细胞因子风暴有关。然而，宿主炎症反应和SARS-CoV-2感染之间的相互作用在很大程度上仍然未知。在这里，我们证明了SARS-CoV-2核衣壳（N）蛋白，病毒粒子的主要结构蛋白，促进了病毒触发的NF-κB信号转导的激活。N蛋白与病毒RNA结合后，发生液-液相分离（LLPS），募集NF-κB信号转导的关键激酶TAK 1和IKK复合物，增强NF-κB的活化。LLPS抑制剂1，6-己二醇可减弱N蛋白的相分离，抑制其对NF-κB活化的调节作用。这些结果表明，N蛋白的LLPS提供了诱导NF-κB过度活化的平台，这可能是COVID-19重症肺炎的潜在治疗靶点。
The ongoing 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 has posed a worldwide pandemic and a major global public health threat. The severity and mortality of COVID-19 are associated with virus-induced dysfunctional inflammatory responses and cytokine storms. However, the interplay between host inflammatory responses and SARS-CoV-2 infection remains largely unknown. Here, we demonstrate that SARS-CoV-2 nucleocapsid (N) protein, the major structural protein of the virion, promotes the virus-triggered activation of NF-κB signaling. After binding to viral RNA, N protein robustly undergoes liquid–liquid phase separation (LLPS), which recruits TAK1 and IKK complex, the key kinases of NF-κB signaling, to enhance NF-κB activation. Moreover, 1,6-hexanediol, the inhibitor of LLPS, can attenuate the phase separation of N protein and restrict its regulatory functions in NF-κB activation. These results suggest that LLPS of N protein provides a platform to induce NF-κB hyper-activation, which could be a potential therapeutic target against COVID-19 severe pneumonia.
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影响因子：
9.8
作者：
Jack A;Ferro LS;Trnka MJ;Wehri E;Nadgir A;Nguyenla X;Fox D;Costa K;Stanley S;Schaletzky J;Yildiz A
通讯作者：
Yildiz A
影响因子：
64.5
作者：
Aid M;Busman-Sahay K;Vidal SJ;Maliga Z;Bondoc S;Starke C;Terry M;Jacobson CA;Wrijil L;Ducat S;Brook OR;Miller AD;Porto M;Pellegrini KL;Pino M;Hoang TN;Chandrashekar A;Patel S;Stephenson K;Bosinger SE;Andersen H;Lewis MG;Hecht JL;Sorger PK;Martinot AJ;Estes JD;Barouch DH
通讯作者：
Barouch DH
影响因子：
8.1
作者：
Hojyo S;Uchida M;Tanaka K;Hasebe R;Tanaka Y;Murakami M;Hirano T
通讯作者：
Hirano T
影响因子：
24.8
作者：
Lee, Jeong Seok;Park, Seongwan;Shin, Eui-Cheol
通讯作者：
Shin, Eui-Cheol
影响因子：
4.6
作者：
Cong Y;Kriegenburg F;de Haan CAM;Reggiori F
通讯作者：
Reggiori F