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A Contemporary View of Coronavirus Transcription

Stanley G. Sawicki, Dorothea L. Sawicki, Stuart G. Siddell
Stanley G. Sawicki
1Department of Medical Microbiology and Immunology, University of Toledo College of Medicine, Toledo, Ohio 43614
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Dorothea L. Sawicki
1Department of Medical Microbiology and Immunology, University of Toledo College of Medicine, Toledo, Ohio 43614
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  • For correspondence: dsawicki@meduohio.edu
Stuart G. Siddell
2Department of Molecular and Cellular Medicine, University of Bristol, Bristol BS8 1TD, United Kingdom
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DOI: 10.1128/JVI.01358-06
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  • FIG. 1.
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    FIG. 1.

    Organization and expression of the MHV-A59 genome. The structural relationships of the MHV-A59 genome- and subgenome-length mRNAs are shown. The virus ORFs are depicted in teal (nsp1-nsp16 genes), blue (ns2, ns4a, ns4b, and ns5a genes), and green (S, M, E, N, and I structural protein genes). The ORFs are defined by the genomic sequence of MHV-A59 as published by Coley et al. (20). The open red box represents the common 59-leader sequence, and the barred circle represents the programmed (−1) frameshifting element. The translation products of the genome- and subgenome-length mRNAs are depicted, and the autoproteolytic processing of the ORF1a and ORF1a/ORF1b polyproteins into proteins nsp1 to nsp16 is shown. A number of confirmed and putative functional domains in the nsp proteins are also indicated. NeU, uridylate-specific endoribonuclease; PL1, papain-like protease 1; PL2, papain-like protease 2.

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    FIG. 2.

    Model for coronavirus replication-transcription. The ORF1 of genomic RNA (red) is translated to produce pp1a and pp1ab, which assemble into an RTC (teal oval) that recognizes cis-acting elements at the 5′ and 3′ ends of the genome. This RTC copies the genome either continuously into genome-length template or discontinuously into the various subgenome-length minus-strand templates. The minus strands (blue) are used as templates for genomic and subgenomic mRNA synthesis. Only genomes are used as templates for minus-strand synthesis, i.e., replication. The RTCs engaging in plus-strand synthesis age and release their minus-strand templates, which are then degraded specifically.

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  • TABLE 1.

    Enzymatic activities and characteristics of coronavirus nsp protein domains

    ActivityLocation and designationProtein familyArchitectureCommentsReferences
    Papain-like proteinaseOne or two PLpro domains within nsp3Deubiquitinating enzyme familyFinger-palm-thumbFingertips contain zinc-binding domain 5, 33, 56
    ADP-ribose 1"-phosphataseADRP (or X) domain within nsp3Macro-HS2A-fold familyThree-layered α/β/αAlso found in other plus-strand RNA viruses 53, 58
    3C-like cysteine proteinasensp5 (3CLpro or main protease, Mpro)Two-β-barrel proteinase familyTwelve antiparallel β-strandsExtra, α-helical, carboxyl-terminal domain III 3, 4, 95
    RNA-dependent RNA polymeraseRdRp domain within nsp12Viral RdRp familyFinger-palm-thumb (predicted)RdRp motif VI signature GDD replaced with SDD 19, 87
    5′-to-3′ helicase (associated, NTPase, and RNA 5′-triphosphatase activities)HEL domain within nsp13Superfamily 1 helicaseModeled to Escherichia coli Rep helicaseAdjacent to amino-proximal, binuclear, zinc-binding domain 9, 35, 36, 70
    3′-to-5′ exonucleaseExoN domain within nsp14DEDD superfamilyHexahelical bundle (predicted)Unable to cleave ribose 2′-O-methylated RNA substrates 45, 75
    Uridylate-specific endoribonucleaseNendoU domain within nsp15XendoU familyWing-body-wing (butterfly fold)Active in hexameric form; RNA bound to internal cavity 10, 11, 31, 34, 56a, 88
    S-adenosylmethionine-dependent 2′-O-methyltransferasensp16 (MT)Rrmj methyltransferase familyMethyltransferase fold (predicted)Activity yet to be determined 75, 86
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A Contemporary View of Coronavirus Transcription
Stanley G. Sawicki, Dorothea L. Sawicki, Stuart G. Siddell
Journal of Virology Dec 2006, 81 (1) 20-29; DOI: 10.1128/JVI.01358-06

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A Contemporary View of Coronavirus Transcription
Stanley G. Sawicki, Dorothea L. Sawicki, Stuart G. Siddell
Journal of Virology Dec 2006, 81 (1) 20-29; DOI: 10.1128/JVI.01358-06
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  • Top
  • Article
    • CORONAVIRUS RNA REPLICATION AND TRANSCRIPTION
    • PROTEINS INVOLVED IN CORONAVIRUS TRANSCRIPTION
    • GENETICS OF CORONAVIRUS TRANSCRIPTION
    • ROLE OF THE N PROTEIN
    • WHY IS CORONAVIRUS TRANSCRIPTION SO COMPLEX?
    • ADDENDUM IN PROOF
    • ACKNOWLEDGMENTS
    • REFERENCES
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KEYWORDS

coronavirus
Models, Genetic
Transcription, Genetic

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