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

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  • Fritch, E.J.
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Sanders, W.
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Sims, A.C.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Herring, L.E.
    • Affiliation: School of Medicine, Department of Pharmacology
  • Barker, N.K.
    • Affiliation: School of Medicine, Department of Pharmacology
  • Schepmoes, A.A.
    • Other Affiliation: Pacific Northwest National Laboratory
  • Weitz, K.K.
    • Other Affiliation: Pacific Northwest National Laboratory
  • Texier, J.R.
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Dittmer, D.P.
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Graves, L.M.
    • Affiliation: School of Medicine, Department of Pharmacology
  • Smith, R.D.
    • Other Affiliation: Pacific Northwest National Laboratory
  • Waters, K.M.
    • Other Affiliation: Pacific Northwest National Laboratory
  • Moorman, N.J.
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Baric, R.S.
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Graham, R.L.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
Abstract
  • 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.
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  • Article
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  • In Copyright
License
  • Attribution-NonCommercial-NoDerivs 4.0 International
Journal title
  • iScience
Journal volume
  • 26
Journal issue
  • 6
Language
  • English
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  • Publisher
Funder
  • National Institutes of Health, NIH: T32 AI007419, U19 AI106772, U19 AI107810
  • University of North Carolina, UNC
ISSN
  • 2589-0042
Publisher
  • Elsevier Inc.

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