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RNA-induced liquid phase separation of SARS-CoV-2 nucleocapsid protein facilitates NF-κB hyper-activation and inflammation
- Source :
- Signal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-13 (2021)
- Publication Year :
- 2021
- Publisher :
- Nature Publishing Group, 2021.
-
Abstract
- Abstract 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.
- Subjects :
- Medicine
Biology (General)
QH301-705.5
Subjects
Details
- Language :
- English
- ISSN :
- 20593635
- Volume :
- 6
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Signal Transduction and Targeted Therapy
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.61befcd65460397cf4543a9541513
- Document Type :
- article
- Full Text :
- https://doi.org/10.1038/s41392-021-00575-7