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

Luo, Lingling; Li, Zhean; Zhao, Tiejun; Ju, Xiaohui; Ma, Peixiang; Jin, Bo-Xing; Zhou, Yulin; He, Su; Huang, Jinhua; Xu, Xun; Zou, Yan; Li, Ping; Liang, Aibin; Liu, Jia; Tian, Chao; Huang, Xingxu; Ding, Qiang; Jin, Zhigang; Huang, Cheng; Zhang, Yu

doi:10.1016/j.scib.2021.01.013

Cited by 104 publications

(183 citation statements)

References 53 publications

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“…Stress granules are frequently observed upon infection with DNA or RNA viruses, serving an antiviral function [12,13]. Recent studies reveal that SARS-CoV-2 N protein is associated with SGs and regulates their dynamics [22,[26][27][28]. To investigate whether arginine methylation regulates the property of SARS-CoV-2 N protein to suppress SG formation and dynamics, we monitored SG formation using anti-G3BP1 antibodies in the hepatoma Huh-7, a cell line frequently used in the study of SARS-CoV-2.…”

Section: Sars-cov-2 N Prevents Sg Formation In An Arginine Methylation Dependent Mannermentioning

confidence: 99%

“…The SG nucleating factor G3BP1 [15,16] and other SG components were identified in the SARS-CoV-2 N protein interactome [5,17], suggesting SARS-CoV-2 like SARS-CoV regulates SGs mainly through N protein. The SARS-CoV-2 N protein is able to form condensates with RNA in vitro [18][19][20][21][22][23][24][25], in the cytoplasm of cells [21,25] and partially co-localizes within arsenite-induced SGs [26]. Several studies have shown that N protein sequesters G3BP1 and disassembles SGs [22,[26][27][28], likely as a means to suppress the host immune response to favor virus replication.…”

Section: Introductionmentioning

confidence: 99%

“…The SARS-CoV-2 N protein is able to form condensates with RNA in vitro [18][19][20][21][22][23][24][25], in the cytoplasm of cells [21,25] and partially co-localizes within arsenite-induced SGs [26]. Several studies have shown that N protein sequesters G3BP1 and disassembles SGs [22,[26][27][28], likely as a means to suppress the host immune response to favor virus replication. Recent studies show that IDR1 and NTD regulate N protein condensates affecting nucleic acid annealing and potentially implicated in viral packaging and assembly [21,22,25].…”

Section: Introductionmentioning

confidence: 99%

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Arginine methylation of SARS-Cov-2 nucleocapsid protein regulates RNA binding, its ability to suppress stress granule formation, and viral replication

Cai

Wang

et al. 2021

Journal of Biological Chemistry

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Sars-cov-2 N Prevents Sg Formation In An Arginine Methylation Dependent Mannermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Arginine methylation of SARS-Cov-2 nucleocapsid protein regulates RNA binding, its ability to suppress stress granule formation, and viral replication

Cai

Wang

et al. 2021

Journal of Biological Chemistry

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“…Recent publications have reported that SARS-CoV-2 N induces stress granule disassembly 46,47 . but the mechanistic basis of this is unclear.…”

mentioning

confidence: 99%

Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities

Kruse

Benz

Garvanska

et al. 2021

Preprint

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Viral proteins make extensive use of short peptide interaction motifs to hijack cellular host factors. However, most current large-scale methods do not identify this important class of protein-protein interactions. Uncovering peptide mediated interactions provides both a molecular understanding of viral interactions with their host and the foundation for developing novel antiviral reagents. Here we describe a scalable viral peptide discovery approach covering 229 RNA viruses that provides high resolution information on direct virus-host interactions. We identify 269 peptide-based interactions for 18 coronaviruses including a specific interaction between the human G3BP1/2 proteins and an [FILV]xFG peptide motif in the SARS-CoV-2 nucleocapsid (N) protein. This interaction supports viral replication and through its [FILV]xFG motif N rewires the G3BP1/2 interactome to disrupt stress granules. A peptide-based inhibitor disrupting the G3BP1/2-N interaction blocks SARS-CoV-2 infection showing that our results can be directly translated into novel specific antiviral reagents.

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“…Some of the results with highest significance were discussed in previous reports. An example is represented by the nucleocapsid protein (N) targeting, G3BP1 and G3BP2, which disassemble stress granules and facilitate viral production [26]. In addition, the interactor list is also enriched for proteins that are functionally close to the process of viral entry and to proteins involved in glycolysis and gluconeogenesis.…”

Section: Exploring the Function Of Sars-cov2 Interacting Proteinsmentioning

confidence: 99%

A Resource for the Network Representation of Cell Perturbations Caused by SARS-CoV-2 Infection

Perfetto

Micarelli

Iannuccelli

et al. 2021

Genes

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The coronavirus disease 2019 (COVID-19) pandemic has caused more than 2.3 million casualties worldwide and the lack of effective treatments is a major health concern. The development of targeted drugs is held back due to a limited understanding of the molecular mechanisms underlying the perturbation of cell physiology observed after viral infection. Recently, several approaches, aimed at identifying cellular proteins that may contribute to COVID-19 pathology, have been reported. Albeit valuable, this information offers limited mechanistic insight as these efforts have produced long lists of cellular proteins, the majority of which are not annotated to any cellular pathway. We have embarked in a project aimed at bridging this mechanistic gap by developing a new bioinformatic approach to estimate the functional distance between a subset of proteins and a list of pathways. A comprehensive literature search allowed us to annotate, in the SIGNOR 2.0 resource, causal information underlying the main molecular mechanisms through which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and related coronaviruses affect the host–cell physiology. Next, we developed a new strategy that enabled us to link SARS-CoV-2 interacting proteins to cellular phenotypes via paths of causal relationships. Remarkably, the extensive information about inhibitors of signaling proteins annotated in SIGNOR 2.0 makes it possible to formulate new potential therapeutic strategies. The proposed approach, which is generally applicable, generated a literature-based causal network that can be used as a framework to formulate informed mechanistic hypotheses on COVID-19 etiology and pathology.

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

Cited by 104 publications

References 53 publications

Arginine methylation of SARS-Cov-2 nucleocapsid protein regulates RNA binding, its ability to suppress stress granule formation, and viral replication

Arginine methylation of SARS-Cov-2 nucleocapsid protein regulates RNA binding, its ability to suppress stress granule formation, and viral replication

Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities

A Resource for the Network Representation of Cell Perturbations Caused by SARS-CoV-2 Infection

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