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PXD042148

PXD042148 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA viral pan-end RNA element and host complex define a SARS-CoV-2 regulon
DescriptionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, generates multiple protein-coding, subgenomic RNAs (sgRNAs) from a longer genomic RNA, all bearing identical termini with poorly understood roles in regulating viral gene expression. Insulin and interferon-gamma, two host-derived, stress-related agents, and virus spike protein, induce binding of glutamyl-prolyl-tRNA synthetase (EPRS1), within an unconventional, tetra-aminoacyl-tRNA synthetase complex, to the sgRNA 3'end thereby enhancing sgRNA expression. We identify an EPRS1-binding sarbecoviral pan-end activating RNA (SPEAR) element in the 3'end of viral RNAs driving agonist-induction. Translation of another co-terminal 3'end feature, ORF10, is necessary for SPEAR-mediated induction, independent of Orf10 protein expression. The SPEAR element enhances viral programmed ribosomal frameshifting, thereby expanding its functionality. By co-opting noncanonical activities of a family of essential host proteins, the virus establishes a post-transcriptional regulon stimulating global viral RNA translation. A SPEAR-targeting strategy markedly reduces SARS-CoV-2 titer and kinetics, suggesting a pan-sarbecoviral therapeutic modality.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_09:01:04.631.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD042148
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterLing Li
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-05-11 07:14:41ID requested
12023-06-12 09:39:14announced
22023-11-14 09:01:05announced2023-11-14: Updated project metadata.
Publication List
10.6019/PXD042148;
Keyword List
submitter keyword: SARS-CoV-2
COVID-19
translational control
RNA element
RNA-binding protein
EPRS1
aminoacyl-tRNA synthetase
multi-tRNA synthetase complex
post-transcriptional regulon
3’ untranslated region
obesity
insulin
interferon-gamma
spike protein
subgenomic RNA
programmed ribosomal frameshifting
SPEAR element
ORF10
3’end
SARS-CoV-2 replicon
PPMO
Contact List
Paul L Fox
contact affiliationDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
contact emailfoxp@ccf.org
lab head
Ling Li
contact affiliationCleveland Clinic
contact emaillil5@ccf.org
dataset submitter
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Dataset FTP location
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