Title
SARS-CoV-2 expresses a microRNA-like small RNA able to selectively repress host genes
Date Issued
28 December 2021
Access level
open access
Resource Type
journal article
Author(s)
Yale University School of Medicine
Publisher(s)
National Academy of Sciences
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19), continues to be a pressing health concern. In this study, we investigated the impact of SARS-CoV-2 infection on host microRNA (miRNA) populations in three human lung-derived cell lines, as well as in nasopharyngeal swabs from SARS-CoV-2-infected individuals. We did not detect any major and consistent differences in host miRNA levels after SARS-CoV-2 infection. However, we unexpectedly discovered a viral miRNA-like small RNA, named CoV2-miR-O7a (for SARS-CoV-2 miRNA-like ORF7a-derived small RNA). Its abundance ranges from low to moderate as compared to host miRNAs and it associates with Argonaute proteins-core components of the RNA interference pathway. We identify putative targets for CoV2-miRO7a, including Basic Leucine Zipper ATF-Like Transcription Factor 2 (BATF2), which participates in interferon signaling. We demonstrate that CoV2-miR-O7a production relies on cellular machinery, yet is independent of Drosha protein, and is enhanced by the presence of a strong and evolutionarily conserved hairpin formed within the ORF7a sequence.
Volume
118
Issue
52
Language
English
OCDE Knowledge area
Biología celular, Microbiología
Bioquímica, Biología molecular
Virología
Subjects
Scopus EID
2-s2.0-85122597482
PubMed ID
Source
Proceedings of the National Academy of Sciences of the United States of America
ISSN of the container
00278424
DOI of the container
10.1073/pnas.2116668118
Sponsor(s)
This work was funded by the NIH supplement 3P01CA016038-45S1 (to J.A.S.), by NIH grant R01GM133810 grant (to W.N.M.), and by the Yale School of Medicine Department of InternalMedicine, the Prostate Cancer Foundation, the Harrington Discovery Institute, and the COVID-19 Early Treatment Fund (to J.M.V.). P.P. was supported by NIH fellowship K99/R00 (K99GM129412/R00GM129412). J.A.S.was an Investigator of the Howard HughesMedical Institute.
ACKNOWLEDGMENTS. We thank the members of the J.A.S. laboratory for advice and support. We are grateful to Dr. Craig Wilen for the help in setting up BSL3 work. We thank Dr. Charles Rice for Hu7.5 cells and Huh7.5 Drosha knockout cells. We are grateful to Dr. Benjamin Goldman-Israelow for a plasmid expressing hACE2. We acknowledge the hard work of Yale’s Environmental Health and Safety program, in particular Benjamin Fontes. We appreciate Germano Cecere’s sharing of comparable findings prior to publication. This work was funded by the NIH supplement 3P01CA016038-45S1 (to J.A.S.), by NIH grant R01GM133810 grant (to W.N.M.), and by the Yale School of Medicine Department of Internal Medicine, the Prostate Cancer Foundation, the Harring-ton Discovery Institute, and the COVID-19 Early Treatment Fund (to J.M.V.). P.P. was supported by NIH fellowship K99/R00 (K99GM129412/R00GM129412). J.A.S. was an Investigator of the Howard Hughes Medical Institute.
Sources of information:
Directorio de Producción Científica
Scopus