PXD031611 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Depletion of EXOSC2 protects against clinical COVID-19 and impedes SARS-CoV-2 replication |
Description | New therapeutic targets are a valuable resource in the struggle to reduce the morbidity and mortality associated with the COVID-19 pandemic. Genome-wide association studies (GWAS) have identified a number of risk loci but these include co-morbidities and are not specific to host-virus interactions. Here, we identify and experimentally validate a link between reduced expression of EXOSC2 and reduced SARS-CoV-2 replication. We identified lung-specific eQTLs from GTEx (v7) for 332 host proteins which directly interact with SARS-CoV-2 proteins. Aggregating COVID-19 GWAS statistics for gene-specific eQTLs revealed a robust association between increased expression of EXOSC2 and higher risk of clinical COVID-19. EXOSC2 is a component of the RNA exosome and further LC-MS/MS analysis of protein pulldowns demonstrated an interaction between the SARS-CoV-2 RNA polymerase and the majority of RNA exosome components. CRISPR/Cas9 introduction of nonsense mutations within EXOSC2 in Calu3 cells reduced EXOSC2 protein expression, impeded SARS-CoV-2 replication and upregulated OAS genes which have been linked to a successful immune response against SARS-CoV-2. OAS gene expression changes occurred independent of infection, in the absence of significant upregulation of other interferon-stimulated genes (ISGs), and did not coincide with reduced cellular viability. Targeted depletion or functional inhibition of EXOSC2 may be a safe and effective strategy to protect at-risk individuals against clinical COVID-19. |
HostingRepository | PRIDE |
AnnounceDate | 2022-10-13 |
AnnouncementXML | Submission_2022-10-13_02:22:01.039.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | MarkCollins |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap Elite |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-02-11 06:20:20 | ID requested | |
⏵ 1 | 2022-10-13 02:22:01 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: SARS-CoV-2, viral replication, EXOSC2 |
Contact List
MarkCollins |
contact affiliation | School of Biosciences Firth Court, Western Bank University of Sheffield Sheffield, S10 2TN |
contact email | mark.collins@sheffield.ac.uk |
lab head | |
MarkCollins |
contact affiliation | University of Sheffield |
contact email | mark.collins@sheffield.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD031611
- Label: PRIDE project
- Name: Depletion of EXOSC2 protects against clinical COVID-19 and impedes SARS-CoV-2 replication