SARS-CoV-2 expresses a microRNA-like small RNA able to selectively repress host genes

Paulina Pawlica, Therese A. Yario, Sylvia White, Jianhui Wang, Walter N. Moss, Pei Hui, Joseph M. Vinetz, Joan A. Steitz

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

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.

Original languageEnglish
Article numbere2116668118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number52
DOIs
StatePublished - 28 Dec 2021
Externally publishedYes

Keywords

  • MicoRNA
  • Noncoding RNA
  • SARS-CoV-2

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