Evidence map›Paper›PMID 37296097›Full record

ArticleNature communications2023

A viral pan-end RNA element and host complex define a SARS-CoV-2 regulon.

Debjit Khan, Fulvia Terenzi, GuanQun Liu, Prabar K Ghosh, Fengchun Ye, Kien Nguyen, Arnab China, Iyappan Ramachandiran, Shruti Chakraborty, Jennifer Stefan and 7 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.2field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 14 citations in OpenAlex.

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  7. AKT-dependent nuclear localization of EPRS1 activates PARP1 in breast cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 2 institutions in 1 country.

Debjit KhanDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.ORCID 0000-0001-5568-3361
Fulvia TerenziDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
GuanQun LiuFlorida Research and Innovation Center, Cleveland Clinic Foundation, Port St. Lucie, FL, 34987, USA.ORCID 0000-0003-2520-7625
Prabar K GhoshDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
Fengchun YeDepartment of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA.ORCID 0000-0002-2085-0884
Kien NguyenDepartment of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA.
Arnab ChinaDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
Iyappan RamachandiranDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
Shruti ChakrabortyDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
Jennifer StefanDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
Krishnendu KhanDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
Kommireddy VasuDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
Franklin DongDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.ORCID 0000-0002-9821-3551
Belinda WillardLerner Research Institute Proteomics and Metabolomics Core, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
Jonathan KarnDepartment of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA.ORCID 0000-0002-2900-094X
Michaela U GackFlorida Research and Innovation Center, Cleveland Clinic Foundation, Port St. Lucie, FL, 34987, USA.ORCID 0000-0002-2163-2598
Paul L FoxDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA. foxp@ccf.org.ORCID 0000-0002-6033-1528
Cleveland Clinic · USCase Western Reserve University · US

Funding

TUMOR METABOLISM PROGRAMP30CA043703 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI Amar Desai · 1987 to 2026
$142.3M
Regulation of Host Innate Immunity Against Viral InfectionR37AI087846 · NIAID · CLEVELAND CLINIC LERNER COM-CWRU · PI Michaela Ulrike Gack · 2021 to 2026
$2.8M
Childhood-onset hypomyelinating leukodystrophy and the multi-tRNA synthetase complexR01NS124581 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI Ranjan Dutta, PAUL L FOX · 2023 to 2026
$2.5M
Adipokines, Aging, and Alzheimers DiseaseR01AG067146 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI FOX, PAUL L · 2020 to 2024
$2.4M
The mammalian multi-tRNA synthetase complexR01NS124547 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI PAUL L FOX, Valentin Gogonea · 2022 to 2026
$2.4M
The Untranslated 3'End of SARS-CoV-2 RNA as a Determinant of Obesity-Accelerated InfectivityR01DK130377 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI FOX, PAUL L · 2021 to 2023
$1.2M
Assay Development for Discovery of a Small Molecule Inhibitor of a Novel Metabolic Pathway that Drives ObesityR01DK124203 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI FOX, PAUL L · 2020 to 2022
$1.2M
Leica TCS SP8 Confocal Microscope for a Core FacilityS10OD019972 · OD · CLEVELAND CLINIC LERNER COM-CWRU · PI DRAZBA, JUDY · 2015 to 2015
$544k
NCI NIH HHS P30 CA043703NIAID NIH HHS R37 AI087846NIA NIH HHS R01 AG067146NIDDK NIH HHS R01 DK124203NIDDK NIH HHS R01 DK130377NIH HHS S10 OD019972NINDS NIH HHS R01 NS124547NINDS NIH HHS R01 NS124581
6 · The paper itself

Abstract

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, suggesting a pan-sarbecoviral therapeutic modality.

Indexed as

RegulonRNA, ViralSARS-CoV-2Subgenomic RNACOVID-19HumansViral ProteinsRNA, ViralSubgenomic RNAViral Proteins

Identifiers

PMID37296097
PMCPMC10250186
OpenAlexW4380027832

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.