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

Cai, Ting; Yu, Zhenbao; Wang, Zhen; Liang, Chen; Richard, Stéphane

doi:10.1016/j.jbc.2021.100821

Cited by 56 publications

(86 citation statements)

References 100 publications

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“…Most of the overlapping hits were present in AP-MS studies and involved in ribosome biogenesis and RNA process (for example FBL, BMS1, NOP56, BOP1, WDR12, DHX37 and DDX54) and immune response (for example, MOV10, EIF2AK2, TARBP2, TRIM25, HERC5 and ZCCHC3) (Table S3). It is important to note that two stress granule proteins, G3BP1 and G3BP2, were most consistently identified in other studies [4][5][6][7][8]15,[26][27][28][29]. G3BP1 and G3BP2 are downregulated during SARS-CoV-2 infection, and inhibition of stress granule formation by the N protein indicates that the N protein is involved in suppressing the host immune response to favour virus replication [5,30].…”

Section: Comparison Of the N Protein Interactome With Other Sars-cov-2-induced Proteomes And Transcriptomesmentioning

confidence: 75%

“…It is important to note that two stress granule proteins, G3BP1 and G3BP2, were most consistently identified in other studies [4][5][6][7][8]15,[26][27][28][29]. G3BP1 and G3BP2 are downregulated during SARS-CoV-2 infection, and inhibition of stress granule formation by the N protein indicates that the N protein is involved in suppressing the host immune response to favour virus replication [5,30].…”

Section: Comparison Of the N Protein Interactome With Other Sars-cov-2-induced Proteomes And Transcriptomesmentioning

confidence: 75%

“…We identified 17 shared human proteins in HEK293T and Calu-3 cells (Table 1), including ribosome biogenesis proteins BOP1, MRPL22, RRP15, NOP16, NOP10 and NHP2; RNA catalytic proteins POLRMT and POLR1G; virus defence proteins G3BP1, G3BP2, ZC3HAV1 and TRIM25, and various others. Five of the overlapping proteins, G3BP1, G3BP2, BOP1, ZNF346 and TRIM25 have been present in previous studies [4][5][6][7][8]15]. TRIM25 is an E3 ubiquitin ligase, which activates the type I interferon (IFN) pathway through the ubiquitination of RIG-I and ZC3HAV1 [16,17].…”

Section: Identification Of Host Factors That Interact With Sars-cov-2 N Protein In Hek293t and Calu-3 Cellsmentioning

confidence: 98%

“…In response, host cells employ antiviral defences through the PPI network. Several individual proteomic studies have mapped the PPI network between SARS-CoV-2 proteins and human proteins, extending our knowledge of viral pathogenesis [4][5][6][7][8]. Given the multiple functions of the N protein, and its high expression during SARS-CoV-2 infections, we applied a systematic affinity tag purification and mass spectrometry (AP-MS) approach to identify host proteins Pathogens 2021, 10, 1155 2 of 12 that interact with the nucleocapsid protein of SARS-CoV-2.…”

Section: Introductionmentioning

confidence: 99%

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Interactome Analysis of the Nucleocapsid Protein of SARS-CoV-2 Virus

Zheng

Sun

et al. 2021

Pathogens

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SARS-CoV-2 infection has caused a global pandemic that has severely damaged both public health and the economy. The nucleocapsid protein of SARS-CoV-2 is multifunctional and plays an important role in ribonucleocapsid formation and viral genome replication. In order to elucidate its functions, interaction partners of the SARS-CoV-2 N protein in human cells were identified via affinity purification and mass spectrometry. We identified 160 cellular proteins as interaction partners of the SARS-CoV-2 N protein in HEK293T and/or Calu-3 cells. Functional analysis revealed strong enrichment for ribosome biogenesis and RNA-associated processes, including ribonucleoprotein complex biogenesis, ribosomal large and small subunits biogenesis, RNA binding, catalysis, translation and transcription. Proteins related to virus defence responses, including MOV10, EIF2AK2, TRIM25, G3BP1, ZC3HAV1 and ZCCHC3 were also identified in the N protein interactome. This study comprehensively profiled the viral–host interactome of the SARS-CoV-2 N protein in human cells, and the findings provide the basis for further studies on the pathogenesis and antiviral strategies for this emerging infection.

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Section: Comparison Of the N Protein Interactome With Other Sars-cov-2-induced Proteomes And Transcriptomesmentioning

confidence: 75%

Section: Comparison Of the N Protein Interactome With Other Sars-cov-2-induced Proteomes And Transcriptomesmentioning

confidence: 75%

Section: Identification Of Host Factors That Interact With Sars-cov-2 N Protein In Hek293t and Calu-3 Cellsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Interactome Analysis of the Nucleocapsid Protein of SARS-CoV-2 Virus

Zheng

Sun

et al. 2021

Pathogens

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“…G3BP2 is involved in stress granule formation and documented to be inhibited by SARS-CoV-2 nucleocapsid protein. [69,70] Cleavage of RNA cleavage factor Im subunits CPSF5/7 likely contributes to enhanced viral RNA translation by trapping host pre-mRNA in the nucleus as with influenza virus. [71] ZFC3H1 is a subunit of the poly(A) tail exosome targeting (PAXT) complex which targets longer and more polyadenylated RNAs than the traditional nuclear exosome targeting (NEXT) complex [72] with subunit ZCCHC14 also cleaved by PLpro and others cleaved by 3CLpro.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 PLpro whole human proteome cleavage prediction and enrichment/depletion analysis

Prescott¹

2021

Preprint

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A novel coronavirus (SARS-CoV-2) has caused a pandemic that has killed millions of people, worldwide vaccination and herd immunity are still far away, and few therapeutics are approved by regulatory agencies for widespread use. The coronavirus 3-chymotrypsin-like protease (3CLpro) is a commonly investigated target in COVID-19, however less work has been directed toward the equally important papain-like protease (PLpro). PLpro is less characterized due to its fewer and more diverse cleavages in coronavirus proteomes and the assumption that it mainly modulates host pathways with its deubiquitinating activity. Here, I extend my previous work on 3CLpro human cleavage prediction and enrichment/depletion analysis to PLpro. Using three sets of neural networks trained on different taxonomic ranks of dataset with a maximum of 463 different putative PLpro cleavages, Matthews correlation coefficients of 0.900, 0.948, and 0.966 were achieved for Coronaviridae, Betacoronavirus, and Sarbecovirus, respectively. I predict that more than 1,000 human proteins may be cleaved by PLpro depending on diversity of the training dataset and that many of these proteins are distinct from those previously predicted to be cleaved by 3CLpro. PLpro cleavages are similarly nonrandomly distributed and result in many annotations shared with 3CLpro cleavages including ubiquitination, poly(A) tail and 5' cap RNA binding proteins, helicases, and endogenous viral proteins. Combining PLpro with 3CLpro cleavage predictions, additional novel enrichment analysis was performed on known substrates of cleaved E3 ubiquitin ligases with results indicating that many pathways including viral RNA sensing are affected indirectly by E3 ligase cleavage independent of traditional PLpro deubiquitinating activity. As with 3CLpro, PLpro whole proteome cleavage prediction revealed many novel potential therapeutic targets against coronaviruses, although experimental verification is similarly required.

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Long noncoding RNA expression analysis in Crimean Congo hemorrhagic fever patients

Arslan

Bakır

Bayyurt

et al. 2022

Journal of Medical Virology

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Crimean Congo hemorrhagic fever (CCHF) is an acute viral infection that can cause death. The detection of host transcriptome is important for understanding differences in the pathogenesis of the disease. Long noncoding RNAs (lncRNAs) regulate gene expression in different biological processes. They have also emerged as key molecules for therapeutic targets. We investigated the lncRNA gene expression profiles by utilizing the microarray for the first time in CCHF. LncRNAs were determined by the comparisons between case-control, fatal case-control, and fatal case-nonfatal cases. Quantitative polymerase chain reaction was applied to validate the microarray results of some lncRNAs. In our study, 39 lncRNAs (5 downregulated and 34 upregulated) were found to be significantly regulated in the cases when compared to the controls (p < 0.05; FC ≥ 2). One hundred ten lncRNAs exhibited a statistically significant difference between fatal cases and controls. FER1L4, ECRP, and LOC100133669 are important lncRNAs in both case and fatal case groups compared with controls. These lncRNAs may be considered important therapeutic targets for the CCHF in further studies.

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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

Cited by 56 publications

References 100 publications

Interactome Analysis of the Nucleocapsid Protein of SARS-CoV-2 Virus

Interactome Analysis of the Nucleocapsid Protein of SARS-CoV-2 Virus

SARS-CoV-2 PLpro whole human proteome cleavage prediction and enrichment/depletion analysis

Long noncoding RNA expression analysis in Crimean Congo hemorrhagic fever patients

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