PXD042148 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | A viral pan-end RNA element and host complex define a SARS-CoV-2 regulon |
Description | Severe 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. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_09:01:04.631.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD042148 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Ling Li |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-05-11 07:14:41 | ID requested | |
1 | 2023-06-12 09:39:14 | announced | |
⏵ 2 | 2023-11-14 09:01:05 | announced | 2023-11-14: Updated project metadata. |
Publication List
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 affiliation | Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA |
contact email | foxp@ccf.org |
lab head | |
Ling Li |
contact affiliation | Cleveland Clinic |
contact email | lil5@ccf.org |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD042148
- Label: PRIDE project
- Name: A viral pan-end RNA element and host complex define a SARS-CoV-2 regulon