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PXD018328-2

PXD018328 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleHuman cytomegalovirus long non-coding RNA1.2 suppresses extracellular release of the pro-inflammatory cytokine IL-6 by blocking NF-κB activation
DescriptionLong non-coding RNAs (lncRNAs) are transcripts of more than 200 nucleotides that are not translated into functional proteins. Cellular lncRNAs have been shown to act as regulators by interacting with target nucleic acids or proteins and modulating their activities. We investigated the role of RNA1.2, which is one of four major lncRNAs expressed by human cytomegalovirus (HCMV), by comparing the properties of parental virus in vitro with those of deletion mutants lacking either most of the RNA1.2 gene or only the TATA element of the promoter. In comparison with parental virus, these mutants exhibited no growth defects and minimal differences in viral gene expression in human fibroblasts. In contrast, 76 cellular genes were consistently up- or down-regulated by the mutants at both the RNA and protein levels at 72 hours after infection. Differential expression of the gene most highly upregulated by the mutants (Tumor protein p63-regulated gene 1-like protein; TPRG1L) was confirmed at both levels by RT-PCR and immunoblotting. Consistent with the known ability of TPRG1L to upregulate IL-6 expression via NF-κB stimulation, RNA1.2 mutant-infected fibroblasts were observed to upregulate IL-6 in addition to TPRG1L. Comparable surface expression of TNF receptors and responsiveness to TNF-α in cells infected by the parental and mutant viruses indicated that activation of signaling by TNF-α is not involved in upregulation of IL-6 by the mutants. In contrast, inhibition of NF-κB activity and knockdown of TPRG1L expression reduced the extracellular release of IL-6 by RNA1.2 mutant-infected cells, thus demonstrating that upregulation of TPRG1L activates NF-κB. The levels of CCL2 and CXCL1 transcripts were also increased in RNA1.2 mutant-infected cells, further demonstrating the presence of active NF-κB signalling. These results suggest that RNA1.2 plays a role in manipulating intrinsic NF-B-dependent cytokine and chemokine release during HCMV infection , thereby impacting downstream immune responses.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:08:38.197.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKatie Nightingale
SpeciesList scientific name: Human herpesvirus 5 strain Merlin; NCBI TaxID: 295027; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-04-01 10:06:43ID requested
12020-07-08 06:20:48announced
22024-10-22 05:08:38announced2024-10-22: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: TPRG1L, IL-6, gene regulation, NF-κB, lncRNA, transcriptomics,human cytomegalovirus
Contact List
Andrew Davison
contact affiliationMRC-University of Glasgow Centre for Virus Research, Sir Michael Stoker Building, Garscube Campus, 464 Bearsden Road, Glasgow G61 1QH, Scotland (UK)
contact emailandrew.davison@glasgow.ac.uk
lab head
Katie Nightingale
contact affiliationCambridge Institute for Medical Research, University of Cambridge
contact emailkln25@cam.ac.uk
dataset submitter
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Dataset FTP location
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