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SARS-CoV-2 Nucleocapsid Protein Impairs SG Assembly by Partitioning into G3BP Condensate

23 Pages Posted: 9 Jul 2020 Publication Status: Review Complete

See all articles by Lingling Luo

Lingling Luo

Shanghai University of Traditional Chinese Medicine - School of Pharmacy

Zhean Li

ShanghaiTech University - School of Life Science and Technology

Peixiang Ma

ShanghaiTech University - Shanghai Institute for Advanced Immunochemical Studies

Yan Zou

ShanghaiTech University - Shanghai Institute for Advanced Immunochemical Studies

Ping Li

Tongji University - Department of Hematology

Aibin Liang

Tongji University - Department of Hematology

Zhigang Jin

Zhejiang University - College of Chemistry and Life Sciences

Tian Chi

ShanghaiTech University - School of Life Science and Technology

Cheng Huang

Shanghai University of Traditional Chinese Medicine - Drug Discovery Lab

Yu Zhang

ShanghaiTech University - School of Life Science and Technology

Xingxu Huang

ShanghaiTech University - School of Life Science and Technology

More...

Abstract

SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), has posed a huge threat to global health and economy. A key to tackle this pandemic is to understand how SARS-CoV-2 manages to outsmart antiviral defense mechanisms. Stress granules (SGs), assembled during stress and functioning to sequester mRNA, are part of the antiviral response. Here, we show the SARS-CoV-2 N protein, an RNA binding protein involved in viral RNA replication and transcription, interacts with RNA-binding protein G3BP (the core proteins in SGs) and inhibits SG assembly in vivo, both effects requiring the RNA binding domain in N protein. Furthermore, N protein undergoes liquid-liquid phase separation (LLPS) and partitions into G3BP droplets in an RNA-dependent manner in vitro. This study suggests that N protein-mediated suppression of SG assembly is an important step in the pathogenesis of COVID-19, which has obvious therapeutic implications.

Funding: This work is supported by National Science Foundation of China (81830004) and Local Grant (608285568031).

Conflict of Interest: The authors declare no competing interests.

Ethical Approval: The ShanghaiTech University Research Ethics Committee has approved the proposed project below based on the information provided in the proposal.

Keywords: SARS-CoV-2; Nucleocapsid Protein; Stress Granules; Liquid-Liquid Phase Separation; G3BP

Suggested Citation

Luo, Lingling and Li, Zhean and Ma, Peixiang and Zou, Yan and Li, Ping and Liang, Aibin and Jin, Zhigang and Chi, Tian and Huang, Cheng and Zhang, Yu and Huang, Xingxu, SARS-CoV-2 Nucleocapsid Protein Impairs SG Assembly by Partitioning into G3BP Condensate. Available at SSRN: https://ssrn.com/abstract=3646571 or http://dx.doi.org/10.2139/ssrn.3646571
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Lingling Luo

Shanghai University of Traditional Chinese Medicine - School of Pharmacy ( email )

Shanghai, 201210
China

Zhean Li

ShanghaiTech University - School of Life Science and Technology ( email )

100 Haike Road, Zhangjiang Hi-Tech Park, Pudong
Research Building
Shanghai, 201210
China

Peixiang Ma

ShanghaiTech University - Shanghai Institute for Advanced Immunochemical Studies ( email )

393 Middle Huaxia Road, Pudong
Shanghai, 201210
China

Yan Zou

ShanghaiTech University - Shanghai Institute for Advanced Immunochemical Studies ( email )

393 Middle Huaxia Road, Pudong
Shanghai, 201210
China

Ping Li

Tongji University - Department of Hematology ( email )

Shanghai
China

Aibin Liang

Tongji University - Department of Hematology ( email )

Shanghai
China

Zhigang Jin

Zhejiang University - College of Chemistry and Life Sciences ( email )

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Tian Chi

ShanghaiTech University - School of Life Science and Technology ( email )

100 Haike Road, Zhangjiang Hi-Tech Park, Pudong
Research Building
Shanghai, 201210
China

Cheng Huang

Shanghai University of Traditional Chinese Medicine - Drug Discovery Lab ( email )

Shanghai, 201210
China

Yu Zhang

ShanghaiTech University - School of Life Science and Technology ( email )

100 Haike Road, Zhangjiang Hi-Tech Park, Pudong
Research Building
Shanghai, 201210
China

Xingxu Huang (Contact Author)

ShanghaiTech University - School of Life Science and Technology

100 Haike Road, Zhangjiang Hi-Tech Park, Pudong
Research Building
Shanghai, 201210
China

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