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Proc Natl Acad Sci U S A . SARS-CoV-2 expresses a microRNA-like small RNA able to selectively repress host genes

tetano

Editor, Senior Moderator
Proc Natl Acad Sci U S A


. 2021 Dec 28;118(52):e2116668118.
doi: 10.1073/pnas.2116668118. Epub 2021 Dec 13.
SARS-CoV-2 expresses a microRNA-like small RNA able to selectively repress host genes


Paulina Pawlica[SUP] 1 [/SUP], Therese A Yario[SUP] 2 3 [/SUP], Sylvia White[SUP] 4 [/SUP], Jianhui Wang[SUP] 4 [/SUP], Walter N Moss[SUP] 5 [/SUP], Pei Hui[SUP] 4 [/SUP], Joseph M Vinetz[SUP] 6 [/SUP], Joan A Steitz[SUP] 1 3 [/SUP]



Affiliations

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-miR-O7a, 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.

Keywords: SARS-CoV-2; micoRNA; noncoding RNA.
 
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