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, Krishnendu Khan, Kommireddy Vasu, Franklin Dong, Belinda Willard, Jonathan Karn, Michaela U. Gack and Paul L. Fox ()
Additional contact information
Debjit Khan: Lerner Research Institute, Cleveland Clinic Foundation
Fulvia Terenzi: Lerner Research Institute, Cleveland Clinic Foundation
GuanQun Liu: Cleveland Clinic Foundation
Prabar K. Ghosh: Lerner Research Institute, Cleveland Clinic Foundation
Fengchun Ye: Case Western Reserve University
Kien Nguyen: Case Western Reserve University
Arnab China: Lerner Research Institute, Cleveland Clinic Foundation
Iyappan Ramachandiran: Lerner Research Institute, Cleveland Clinic Foundation
Shruti Chakraborty: Lerner Research Institute, Cleveland Clinic Foundation
Jennifer Stefan: Lerner Research Institute, Cleveland Clinic Foundation
Krishnendu Khan: Lerner Research Institute, Cleveland Clinic Foundation
Kommireddy Vasu: Lerner Research Institute, Cleveland Clinic Foundation
Franklin Dong: Lerner Research Institute, Cleveland Clinic Foundation
Belinda Willard: Lerner Research Institute Proteomics and Metabolomics Core, Cleveland Clinic Foundation
Jonathan Karn: Case Western Reserve University
Michaela U. Gack: Cleveland Clinic Foundation
Paul L. Fox: Lerner Research Institute, Cleveland Clinic Foundation

Nature Communications, 2023, vol. 14, issue 1, 1-22

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-39091-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39091-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-39091-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().