期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：52
DOI：10.1073/pnas.2116668118
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
We discovered that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) expresses a small viral noncoding RNA, named CoV2-miR-O7a (for SARS-CoV-2 miRNA-like ORF7a-derived small RNA). CoV2-miR-O7a associates with the cellular RNA interference machinery and has the potential to regulate host transcripts, likely via target slicing. The production of CoV2-miR-O7a relies on cellular machinery and the formation of a strong hairpin within ORF7a sequences. This newly described CoV2-miR-O7a may contribute to SARS-CoV-2 pathogenesis and could become a target for therapeutic intervention.
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.
