SARS-CoV-2 nucleocapsid protein phase separates with G3BPs to disassemble stress granules and facilitate viral production.

Abstract

A key to tackling the coronavirus disease 2019 (COVID-19) pandemic is to understand how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) manages to outsmart host antiviral defense mechanisms. Stress granules (SGs), which are assembled during viral infection and function to sequester host and viral mRNAs and proteins, are part of the antiviral responses. Here, we show that the SARS-CoV-2 nucleocapsid (N) protein, an RNA binding protein essential for viral production, interacted with Ras-GTPase-activating protein SH3-domain-binding protein (G3BP) and disrupted SG assembly, both of which require intrinsically disordered region1 (IDR1) in N protein. The N protein partitioned into SGs through liquid-liquid phase separation with G3BP, and blocked the interaction of G3BP1 with other SG-related proteins. Moreover, the N protein domains important for phase separation with G3BP and SG disassembly were required for SARS-CoV-2 viral production. We propose that N protein-mediated SG disassembly is crucial for SARS-CoV-2 production.

• Authors: Lingling Luo, Zhean Li, Tiejun Zhao, Xiaohui Ju, Peixiang Ma, Boxing Jin, Yulin Zhou, Su He, Jinhua Huang, Xun Xu, Yan Zou, Ping Li, Aibin Liang, Jia Liu, Tian Chi, Xingxu Huang, Qiang Ding, Zhigang Jin, Cheng Huang, Yu Zhang
• Journal: Science bulletin (Sci Bull (Beijing)) Vol. 66 Issue 12 Pg. 1194-1204 (Jun 30 2021) ISSN: 2095-9273 [Print] Netherlands
• PMID: 33495715 (Publication Type: Journal Article)
• Copyright: © 2021 Science China Press. Published by Elsevier B.V. and Science China Press.