Metatranscriptomics analysis reveals a novel transcriptional and translational landscape during Middle East respiratory syndrome coronavirus infection

• Published in: iScience 2023-06, Vol.26 (6), p.106780, Article 106780
• Main Authors: Fritch, Ethan J., Sanders, Wes, Sims, Amy C., Herring, Laura E., Barker, Natalie K., Schepmoes, Athena A., Weitz, Karl K., Texier, Jordan R., Dittmer, Dirk P., Graves, Lee M., Smith, Richard D., Waters, Katrina M., Moorman, Nathaniel J., Baric, Ralph S., Graham, Rachel L.
• Format: Article
• Language: English
• Subjects: BASIC BIOLOGICAL SCIENCES; Medical microbiology; Transcriptomics; Virology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.106780

Among all RNA viruses, coronavirus RNA transcription is the most complex and involves a process termed “discontinuous transcription” that results in the production of a set of 3′-nested, co-terminal genomic and subgenomic RNAs during infection. While the expression of the classic canonical set of subgenomic RNAs depends on the recognition of a 6- to 7-nt transcription regulatory core sequence (TRS), here, we use deep sequence and metagenomics analysis strategies and show that the coronavirus transcriptome is even more vast and more complex than previously appreciated and involves the production of leader-containing transcripts that have canonical and noncanonical leader-body junctions. Moreover, by ribosome protection and proteomics analyses, we show that both positive- and negative-sense transcripts are translationally active. The data support the hypothesis that the coronavirus proteome is much vaster than previously noted in the literature. [Display omitted] •MERS-CoV produces a complicated network of noncanonical sgmRNAs during replication•Minus-strand translation activity evidence of the MERS-CoV genome and transcripts•Identification of a novel open reading frame within the nucleocapsid coding region Medical microbiology; Virology; Transcriptomics