Molecular determinants for regulation of G3BP1/2 phase separation by the SARS-CoV-2 nucleocapsid protein
Wenjie Huang, Xiaohui Ju, Min Tian, Xiaoyu Li, Yanying Yu, Qingxiang Sun, Qiang Ding, Da Jia
Abstract
The organization and regulation of membraneless compartments in cells remain one of the fundamental questions in biology 1 . How cells harness condensates for their well-being and how pathogens hijack or counteract condensates for their proliferation are elusive. Stress granules (SGs) are dynamic large cytoplasmic phase-separated mRNA-protein condensates in response to various stresses. The assembly of SGs can be positively or negatively regulated by many endogenous or exogenous factors 2 , 3 . G3BP1/2 are the core components of stress granules, which undergoes RNA-dependent liquid–liquid phase separation (LLPS) 2 , 3 . G3BP1/2 interact with a large number of proteins, including Caprin-1 and TIA-1, and both of them promote G3BP1/2-mediated LLPS 2 , 3 . Very recently, G3BP1/2 is shown to interact with the nucleocapsid (N) protein of SARS-CoV-2 4 , 5 , 6 , 7 . In contrast to Caprin-1 and TIA-1, N protein inhibits G3BP1/2-mediated LLPS 4 , 6 . Although the regulation of G3BP1/2-mediated LLPS by N protein is likely to be critical for the SARS-CoV-2 production 6 , the nature of the G3BP1/2-N interaction and the mechanisms underlying the different regulation of G3BP1/2 remain unclear.