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PXD031611-1

PXD031611 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDepletion of EXOSC2 protects against clinical COVID-19 and impedes SARS-CoV-2 replication
DescriptionNew 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.
HostingRepositoryPRIDE
AnnounceDate2022-10-13
AnnouncementXMLSubmission_2022-10-13_02:22:01.039.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMarkCollins
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap Elite
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-02-11 06:20:20ID requested
12022-10-13 02:22:01announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: SARS-CoV-2, viral replication, EXOSC2
Contact List
MarkCollins
contact affiliationSchool of Biosciences Firth Court, Western Bank University of Sheffield Sheffield, S10 2TN
contact emailmark.collins@sheffield.ac.uk
lab head
MarkCollins
contact affiliationUniversity of Sheffield
contact emailmark.collins@sheffield.ac.uk
dataset submitter
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Dataset FTP location
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