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.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19), continues to be a pressing health concern
We discovered that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) expresses a small viral noncoding RNA, named CoV2-miR-O7a
We began by investigating the impact of SARS-CoV-2 infection on host miRNA populations using three human lungderived cell lines and found no consistent changes detected in all three cell lines (Fig. 1C and SI Appendix, Fig. S1C)
Summary
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 the special case where the miRNA is perfectly complementary to its target mRNA, it directs Ago (one of four Ago proteins in humans) to cleave the mRNA target, a function typically associated with small interfering RNAs (siRNAs) [2] Both of these modes of target repression belong to the RNA interference (RNAi) pathway, but Ago2-mediated cleavage is more potent in target silencing and requires lower intracellular copy numbers than the canonical miRNA action mode [3]. 6 and 7) and widespread miRNA polyadenylation by poxvirus poly(A) polymerase, which results in miRNA decay [8] Viruses can produce their own miRNAs, often via noncanonical biogenesis pathways; cytoplasmic viruses especially have devised multiple strategies to bypass the requirement for nuclear Drosha [4, 9]. This newly described CoV2-miR-O7a may contribute to SARSCoV-2 pathogenesis and could become a target for therapeutic intervention
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