Coronavirus Transcription: A Perspective

  • S. G. Sawicki
  • D. L. Sawicki
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 287)


At the VIth International Symposium on Corona and Related Viruses held in Québec, Canada in 1994 we presented a new model for coronavirus transcription to explain how subgenome-length minus strands, which are used as templates for the synthesis of subgenomic mRNAs, might arise by a process involving discontinuous RNA synthesis. The old model explaining subgenomic mRNA synthesis, which was called leader-primed transcription, was based on erroneous evidence that only genome-length negative strands were present in replicative intermediates. To explain the discovery of subgenome-length minus strands, a related model, called the replicon model, was proposed: The subgenomic mRNAs would be produced initially by leader-primed transcription and then replicated into minus-strand templates that would in turn be transcribed into subgenomic mRNAs. We review the experimental evidence that led us to formulate a third model proposing that the discontinuous event in coronavirus RNA synthesis occurs during minus strand synthesis. With our model the genome is copied both continuously to produce minus-strand templates for genome RNA synthesis and discontinuously to produce minus-strand templates for subgenomic mRNA synthesis, and the subgenomic mRNAs do not function as templates for minus strand synthesis, only the genome does.


Strand Synthesis Sindbis Virus Minus Strand Mouse Hepatitis Virus Equine Arteritis Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. An S, Maeda A, Makino S (1998) Coronavirus transcription early in infection. J Virol 72:8517–8524PubMedGoogle Scholar
  2. Baric RS, Stohlman SA, Lai MMC (1983) Characterization of replicative intermediate RNA of mouse hepatitis virus: presence of leader RNA sequences on nascent chains. J Virol 48:633–640PubMedGoogle Scholar
  3. Brayton PR, Lai MMC, Patton CD, Stohlman S (1982) Characterization of two RNA polymerase activities induced by mouse hepatitis virus. J. Virol 42:847–853PubMedGoogle Scholar
  4. Brian DA, Chang RY, Hofmann MA, Sethna PB (1994) Role of subgenomic minusstrand RNA in coronavirus replication. Arch Virol Suppl 9:173–180PubMedGoogle Scholar
  5. Brockway SM, Clay CT, Denison MR (2003) Characterization of the expression, intracellular localization and replication complex association of the putative mouse hepatitis virus RNA-dependent RNA polymerase. J Virol 77:10515–10527CrossRefPubMedGoogle Scholar
  6. Cavanagh D (1997) Nidovirales: a new order comprising Coronaviridae and Arteriviridae. Arch Virol 142:629–633PubMedGoogle Scholar
  7. David-Ferreira JF, Manaker RA (1965) An electron microscope study of the development of a mouse hepatitis virus in tissue culture cells. J Cell Biol 24:57–64CrossRefPubMedGoogle Scholar
  8. Den Boon JA, Spaan WJ, Snijder EJ (1995) Equine arteritis virus subgenomic RNA transcription: UV inactivation and translation inhibition studies. Virology 213:364–372CrossRefPubMedGoogle Scholar
  9. Dobkin C, Mills DR, Kramer FR, Spiegelman S (1979). RNA replication: required intermediates and the dissociation of template, product and the Qbeta replicase. Biochemistry 18:2038–2044CrossRefPubMedGoogle Scholar
  10. Jacobs L, Spaan WJ, Horzinek MC, van der Zeijst BA (1981) Synthesis of subgenomic mRNAs of mouse hepatitis virus is initiated independently: evidence from UV transcription mapping. J Virol 39:401–406PubMedGoogle Scholar
  11. Komissaarova N, Kashlev M (1997a) RNA polymerase switches between inactivated and activated states by translocating back and forth along the DNA and the RNA. J Biol Chem 272:15329–15338CrossRefPubMedGoogle Scholar
  12. Komissaarova N, Kashlev M (1997b) Transcriptional arrest: Escherichia coli RNA polymerase translocates backward, leaving the 3′ end of the RNA intact and extruded. Proc Natl Acad Sci USA 94:1755–1760CrossRefPubMedGoogle Scholar
  13. Kuo L, Master P (2003) The small envelope protein E is not esssential for mouse coronavirus replication. J Virol 77:4597–4608CrossRefPubMedGoogle Scholar
  14. Lai MMC, Patton CD, Baric RS, Stohlman SA (1983) Presence of leader sequences in the mRNA of mouse hepatitis virus. J Virol 46:1027–1033PubMedGoogle Scholar
  15. Lai MMC, Patton CD, Stohlman SA (1982) Replication of mouse hepatitis virus: negative strand RNA and replicative form RNA are of genome length. J Virol 44:487–492PubMedGoogle Scholar
  16. Lai MMC, Baric RS, Brayton PR, Stohlman SA (1984) Characterization of leader RNA sequences on the virion and mRNAs of mouse hepatitis virus, a cytoplasmic RNA virus. Proc Natl Acad Sci USA 81:3626–3630PubMedGoogle Scholar
  17. Lai MMC, Cavanagh D (1997) The molecular biology of coronaviruses. Adv Virus Res 48:1–100CrossRefPubMedGoogle Scholar
  18. Lai MMC, Holmes KV (2001) Coronaviridae: The Viruses and Their Replication. In Fields BN, Knipe DM, Howley PM and Griffin DE (eds). Field's Virology, 4th Edition, volume 1, Lippincott, Williams and Wilkins, Philadelphia.Google Scholar
  19. Lemm JA, Rumenapf T, Strauss EG, Strauss JH, Rice CM (1994) Polypeptide requirements for assembly of functional Sindbis virus replication complexes: a model for temporal regulation of minus strand and plus strand RNA synthesis. EMBO J 13:2925–2934PubMedGoogle Scholar
  20. Makino S, Joo M and Makino JK (1991) A system for study of coronavirus mRNA synthesis: a regulated, expressed subgenomic defective interfering RNA results from intergenic site insertion. J Virol 65:6031–6041PubMedGoogle Scholar
  21. Manaker RA, Piczak CV, Miller AA, Stanton MF (1961) A hepatitis virus complicating studies with mouse leukemia. Natl Cancer Inst 27:29Google Scholar
  22. Masters PS, Koetzner CA, Kerr CA, Heo Y (1994) Optimization of targeted RNA recombination and mapping of novel nucleocapsid gene mutations in the coronavirus mouse hepatitis virus. J Virol 68:328–337PubMedGoogle Scholar
  23. Pasternak AO, van den Born E, Spaan WJ, Snijder EJ (2003) The stability of the duplex between sense and antisense transcription-regulating sequences is a crucial factor in arterivirus subgenomic mRNA synthesis. J Virol 77:1175–1183CrossRefPubMedGoogle Scholar
  24. Sawicki DL, Sawicki SG (1998) Role of the nonstructural polyproteins in alphavirus RNA synthesis. Adv Exp Med Biol 440:187–198PubMedGoogle Scholar
  25. Sawicki SG, Sawicki DL (1986) Coronavirus minus strand synthesis and effect of cycloheximide on coronavirus RNA synthesis. J Virol 57:328–334PubMedGoogle Scholar
  26. Sawicki SG, Sawicki DL (1990) Coronavirus transcription: subgenomic mouse hepatitis virus replicative intermediates function in RNA synthesis. J Virol 64:1050–1056PubMedGoogle Scholar
  27. Sawicki SG, Sawicki DL (1995) Coronaviruses use discontinuous extension for synthesis of subgenome-length negative strands. Adv Exp Med Biol 380:499–506PubMedGoogle Scholar
  28. Sawicki DL, Wang T, Sawicki SG (2001) The RNA structures engaged in replication and transcription of the A59 strain of mouse hepatitis virus. J Gen Virol 82:385–396PubMedGoogle Scholar
  29. Sethna PB, Hofmann MA, Brian DA (1991) Minus-strand copies of replicating coronavirus mRNAs contain antileaders. J. Virol 65:320–325PubMedGoogle Scholar
  30. Sethna PB, Hung SL, Brian DA (1989) Coronavirus subgenomic minus strand RNAs and the potential for mRNA replicons. Proc Natl Acad Sci USA 86:5626–5630PubMedGoogle Scholar
  31. Shaevitz JW, Abbondanzieri EA, Landick R, Block SM (2003) Backtracking by single RNA polymerase molecules observed at near-base-pair resolution. Nature 426:684–687CrossRefPubMedGoogle Scholar
  32. Shirako Y, Strauss JH (1994) Regulation of Sindbis virus RNA replication: uncleaved P123 and nsP4 function in minus strand RNA synthesis, whereas cleaved products from P123 are required for efficient plus strand synthesis. J Virol 68:1874–1885PubMedGoogle Scholar
  33. Siddell SG (1995) The Coronaviridae. Plenum Press, New York.Google Scholar
  34. Simmons DT, Strauss JH (1972) Replication of Sindbis virus II. Multiple forms of double-stranded RNA isolated from infected cells. J Mol Biol 71:615–631PubMedGoogle Scholar
  35. Snijder EJ, Bredenbeek PJ, Dobbe JC, Thiel V, Ziehbuhr J, Poon LL, Guan Y, Rozanov M, Spaan WJ, Gorbalenya AE (2003) Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage. J Mol Biol 331:991–1004CrossRefPubMedGoogle Scholar
  36. Snijder EJ, Meulenberg JJ (1998) The molecular biology of arteriviruses. J Gen Virol 79:961–979PubMedGoogle Scholar
  37. Spaan WJ, Delius H, Skinner M, Armstrong J, Rottier P, Smeekens S, van der Zeijst BA, Siddell SG (1983) Coronavirus mRNA synthesis involves fusion of non-contiguous sequences. EMBO J 2:1839–1844PubMedGoogle Scholar
  38. Stern DF, Sefton BM (1982) Synthesis of coronavirus mRNAs: kinetics of inactivation of infectious bronchititis virus RNA synthesis by UV light. J Virol 42:755–759PubMedGoogle Scholar
  39. Sturman, LS, Takemoto KK (1972) Enhanced growth of a murine coronavirus in transformed mouse cells. Infect Immun 6:501–507PubMedGoogle Scholar
  40. Thiel V, Herold J, Schelle B, Siddell S (2001a) Infectious RNA transcribed in vitro from a cDNA copy of the human coronavirus genome cloned in vaccinia virus. J Gen Virol 82:1273–1281PubMedGoogle Scholar
  41. Thiel V, Herold J, Schelle B, Siddell S. (2001b) Virus replicase gene products suffice for coronavirus discontinuous transcription. J Virol 75:6676–6681CrossRefPubMedGoogle Scholar
  42. Tijms MA, Snijder EJ (2003) Equine arteritis virus non-structural protein 1, an essential factor for viral subgenomic mRNA synthesis, interacts with the cellular transcription co-factor p100. J Gen Virol 84:2317–2322CrossRefPubMedGoogle Scholar
  43. van der Most RG, deGroot RJ, Spaan WJ (1994) Subgenomic RNA synthesis directed by a synthetic defective interfering RNA of mouse hepatitis virus: a study of coronavirus transcription initiation. J Virol 68:3656–3666PubMedGoogle Scholar
  44. van Dinten LC, van Tol H, Gorbalenya AE, Snijder EJ (2000) The predicted metal binding region of the arterivirus helicase protein is involved in subgenomic mRNA synthesis, genome replication and virion biogenesis. J Virol 74:5213–5223CrossRefPubMedGoogle Scholar
  45. van Marle G, Dobbe JC, Gultyaev AP, Luytjes W, Spaan WJ, Snijder EJ (1999a) Arterivirus discontinuous mRNA transcription is guided by base pairing between sense and antisense transcription-regulating sequences. Proc Natl Acad Sci USA 96:12056–12061CrossRefPubMedGoogle Scholar
  46. van Marle G, Luytjes W, van der Most RG, van der Straaten T, Spaan, WJ (1995) Regulation of coronavirus mRNA transcription. J Virol 69:7851–7856PubMedGoogle Scholar
  47. van Marle G, van Dinten LC, Spaan WJ, Lyuytjes W, Snijder EJ (1999b) Characterization of an equine arteritis virus replicase mutant defective in subgenomic mRNA synthesis. J Virol 73:5274–5281PubMedGoogle Scholar
  48. Wang T, Sawicki SG (2001) Mouse hepatitis virus minus strand templates are unstable and turnover during viral replication. Adv Exp Med Biol 494:491–497PubMedGoogle Scholar
  49. Wang YF, Sawicki SG, Sawicki DL (1994) Alphavirus nsP3 functions to form replication complexes transcribing negative strand RNA. J Virol 68:6466–6475PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • S. G. Sawicki
    • 1
  • D. L. Sawicki
    • 1
  1. 1.Department of MicrobiologyMedical College of OhioToledoUSA

Personalised recommendations