Your browser doesn't support javascript.
RNA-induced liquid phase separation of SARS-CoV-2 nucleocapsid protein facilitates NF-κB hyper-activation and inflammation.
Wu, Yaoxing; Ma, Ling; Cai, Sihui; Zhuang, Zhen; Zhao, Zhiyao; Jin, Shouheng; Xie, Weihong; Zhou, Lingli; Zhang, Lei; Zhao, Jincun; Cui, Jun.
  • Wu Y; MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • Ma L; MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • Cai S; MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • Zhuang Z; State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
  • Zhao Z; MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • Jin S; State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
  • Xie W; MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • Zhou L; MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • Zhang L; MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • Zhao J; MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • Cui J; State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China. zhaojincun@gird.cn.
Signal Transduct Target Ther ; 6(1): 167, 2021 04 24.
Article in English | MEDLINE | ID: covidwho-1585891
Semantic information from SemMedBD (by NLM)
1. RNA CAUSES Diastasis
Subject
RNA
Predicate
CAUSES
Object
Diastasis
2. Measles Virus Nucleoprotein PART_OF 2019 novel coronavirus
Subject
Measles Virus Nucleoprotein
Predicate
PART_OF
Object
2019 novel coronavirus
3. Measles Virus Nucleoprotein AUGMENTS positive regulation of NF-kappaB transcription factor activity
Subject
Measles Virus Nucleoprotein
Predicate
AUGMENTS
Object
positive regulation of NF-kappaB transcription factor activity
4. 2019 novel coronavirus CAUSES COVID-19
Subject
2019 novel coronavirus
Predicate
CAUSES
Object
COVID-19
5. Cytokine Storm COEXISTS_WITH Disease
Subject
Cytokine Storm
Predicate
COEXISTS_WITH
Object
Disease
6. Inflammatory Response COEXISTS_WITH Disease
Subject
Inflammatory Response
Predicate
COEXISTS_WITH
Object
Disease
7. Nucleocapsid PART_OF 2019 novel coronavirus
Subject
Nucleocapsid
Predicate
PART_OF
Object
2019 novel coronavirus
8. Structural protein PART_OF Virion
Subject
Structural protein
Predicate
PART_OF
Object
Virion
9. Structural protein AUGMENTS Virus Activation
Subject
Structural protein
Predicate
AUGMENTS
Object
Virus Activation
10. Measles Virus Nucleoprotein INTERACTS_WITH MAP3K7 gene|MAP3K7
Subject
Measles Virus Nucleoprotein
Predicate
INTERACTS_WITH
Object
MAP3K7 gene|MAP3K7
11. NF-kappa B AUGMENTS positive regulation of NF-kappaB transcription factor activity
Subject
NF-kappa B
Predicate
AUGMENTS
Object
positive regulation of NF-kappaB transcription factor activity
12. Measles Virus Nucleoprotein INTERACTS_WITH RN
Subject
Measles Virus Nucleoprotein
Predicate
INTERACTS_WITH
Object
RN
13. hexanediol TREATS Diastasis
Subject
hexanediol
Predicate
TREATS
Object
Diastasis
14. Measles Virus Nucleoprotein CAUSES positive regulation of NF-kappaB transcription factor activity
Subject
Measles Virus Nucleoprotein
Predicate
CAUSES
Object
positive regulation of NF-kappaB transcription factor activity
15. RNA CAUSES Diastasis
Subject
RNA
Predicate
CAUSES
Object
Diastasis
16. Measles Virus Nucleoprotein PART_OF 2019 novel coronavirus
Subject
Measles Virus Nucleoprotein
Predicate
PART_OF
Object
2019 novel coronavirus
17. Measles Virus Nucleoprotein AUGMENTS positive regulation of NF-kappaB transcription factor activity
Subject
Measles Virus Nucleoprotein
Predicate
AUGMENTS
Object
positive regulation of NF-kappaB transcription factor activity
18. 2019 novel coronavirus CAUSES COVID-19
Subject
2019 novel coronavirus
Predicate
CAUSES
Object
COVID-19
19. Cytokine Storm COEXISTS_WITH Disease
Subject
Cytokine Storm
Predicate
COEXISTS_WITH
Object
Disease
20. Inflammatory Response COEXISTS_WITH Disease
Subject
Inflammatory Response
Predicate
COEXISTS_WITH
Object
Disease
21. Nucleocapsid PART_OF 2019 novel coronavirus
Subject
Nucleocapsid
Predicate
PART_OF
Object
2019 novel coronavirus
22. Structural protein PART_OF Virion
Subject
Structural protein
Predicate
PART_OF
Object
Virion
23. Structural protein AUGMENTS Virus Activation
Subject
Structural protein
Predicate
AUGMENTS
Object
Virus Activation
24. Measles Virus Nucleoprotein INTERACTS_WITH MAP3K7 gene|MAP3K7
Subject
Measles Virus Nucleoprotein
Predicate
INTERACTS_WITH
Object
MAP3K7 gene|MAP3K7
25. NF-kappa B AUGMENTS positive regulation of NF-kappaB transcription factor activity
Subject
NF-kappa B
Predicate
AUGMENTS
Object
positive regulation of NF-kappaB transcription factor activity
26. Measles Virus Nucleoprotein INTERACTS_WITH RNA, Viral
Subject
Measles Virus Nucleoprotein
Predicate
INTERACTS_WITH
Object
RNA, Viral
27. hexanediol TREATS Diastasis
Subject
hexanediol
Predicate
TREATS
Object
Diastasis
28. Measles Virus Nucleoprotein CAUSES positive regulation of NF-kappaB transcription factor activity
Subject
Measles Virus Nucleoprotein
Predicate
CAUSES
Object
positive regulation of NF-kappaB transcription factor activity
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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA, Viral / Signal Transduction / NF-kappa B / Coronavirus Nucleocapsid Proteins / SARS-CoV-2 / COVID-19 Limits: Animals / Humans Language: English Journal: Signal Transduct Target Ther Year: 2021 Document Type: Article Affiliation country: S41392-021-00575-7

Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA, Viral / Signal Transduction / NF-kappa B / Coronavirus Nucleocapsid Proteins / SARS-CoV-2 / COVID-19 Limits: Animals / Humans Language: English Journal: Signal Transduct Target Ther Year: 2021 Document Type: Article Affiliation country: S41392-021-00575-7