Murine Coronavirus 5′-End Genomic RNA Sequence Reveals Mechanism of Leader-Primed Transcription

  • Lisa H. Soe
  • Chien-Kou Shieh
  • Shinji Makino
  • Ming-Fu Chang
  • Stephen A. Stohlman
  • Michael M. C. Lai
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 218)


Mouse hepatitis virus (MHV) contains a single-strand, positive-sense RNA genome which is transcribed in infected cells, first, into a full-length negative-strand RNA (Brayton et al., 1982; Lai et al., 1982) and then into a positive-sense genomic RNA and six species of subgenomic mRNA. The mRNAs consist of a 3′ co-terminal nested-set structure (Lai et al., 1981), and also contain an identical leader sequence of approximately 72 nucleotides at the 5′ ends (Lai et al., 1984; Spaan et al., 1983). Ultraviolet transcriptional mapping studies (Jacobs et al., 1981) and the fact that no nuclear function is required for replication (Brayton et al., 1981; Wilhelmsen et al., 1981) suggest that the joining of the leader sequences to coronavirus mRNAs does not utilize conventional eukaryotic splicing mechanisms.


cDNA Clone Leader Sequence Infectious Bronchitis Virus Mouse Hepatitis Virus Avian Infectious Bronchitis Virus 
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  1. Baric, R.S., Stohlman, S.A., and Lai, M.M.C. (1983). Characterization of replicative intermediate RNA of mouse hepatitis virus: Presence of leader RNA sequences on nascent chains. J. Virol. 48, 633–640.PubMedGoogle Scholar
  2. Baric, R.S., Stohlman, S.A., Razavi, M.K., and Lai, M.M.C. (1985). Characterization of leader-related small RNAs in coronavirus-infected cells: Further evidence for leader-primed mechanism of transcription. Virus Res. 3, 19–33.PubMedCrossRefGoogle Scholar
  3. Berg, J.M. (1986). Potential metal-binding domains in nucleic acid binding proteins. Science 232, 485–487.PubMedCrossRefGoogle Scholar
  4. Brayton, P.R., Ganges, R.G., and Stohlman, S.A. (1981). Host cell nuclear function and murine hepatitis virus replication. J. Gen. Virol. 56, 457–460.PubMedCrossRefGoogle Scholar
  5. Brayton, P.R., Lai, M.M.C., Patton, CD., and Stohlman, S.A. (1982). Characterization of two RNA polymerase activities induced by mouse hepatitis virus. J. Virol. 42, 847–853.PubMedGoogle Scholar
  6. Brown, T.D.K., Boursnell, M.E.G., Binns, M.M., and Tomley, F.M. (1986). Cloning and sequencing of 5′ terminal sequences from avian infectious bronchitis virus genomic RNA. J. Gen. Virol. 67, 221–228.PubMedCrossRefGoogle Scholar
  7. Budzilowicz, C.J., Wilczynski, S.P., and Weiss, S.R. (1985). Three intergenic regions of coronavirus mouse hepatitis virus strain A59 genome RNA contain a common nucleotide sequence that is homologous to the 3′ end of the viral mRNA leader sequence. J. Virol. 53, 834–840.PubMedGoogle Scholar
  8. Dagert, M., and Ehrlich, S.D. (1979). Prolonged incubation in calcium chloride improves the competence of Escherichia coli cells. Gene 6, 23–29.PubMedCrossRefGoogle Scholar
  9. Gubler, U., and Hoffman, B.J. (1983). A simple and very efficient method for generating cDNA libraries. Gene 25, 263–269.PubMedCrossRefGoogle Scholar
  10. Henikoff, S., Kelly, J.D., and Cohen, E.H. (1983). Transcription terminates in yeast distal to a control sequence. Cell 33, 607–614.PubMedCrossRefGoogle Scholar
  11. Jacobs, L., Spaan, W.J.M., Horzinek, M.C., and Van der Zeijst, B.A.M. (1981). Synthesis of subgenomic mRNAs of mouse hepatitis virus is initiated independently: Evidence from U.V. transcriptional mapping. J. Virol. 34, 401–406.Google Scholar
  12. Kozak, M. (1983). Comparison of initiation of protein synthesis in procaryotes, eucaryotes, and organelles. Micro. Rev. 47, 1–45.Google Scholar
  13. Lai, M.M.C., Baric, R.S., Brayton, P.R., and Stohlman, S.A. (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, 3626–3630.PubMedCrossRefGoogle Scholar
  14. Lai, M.M.C., Brayton, P.R., Armen, R.C., Patton, CD., Pugh, C, and Stohlman, S.A. (1981). Mouse hepatitis virus A59: mRNA structure and genetic localization of the sequence divergence from hepatotropic strain MHV-3. J. Virol. 39, 823–834.PubMedGoogle Scholar
  15. Lai, M.M.C., Patton, CD., and Stohlman, S.A. (1982). Replication of mouse hepatitis virus: Negative-stranded RNA and replicative form RNA are of genomic length. J. Virol. 44, 487–492.PubMedGoogle Scholar
  16. Leibowitz, J.L., Wilhemsen, K.C., and Bond, C.W. (1981). The virus-specific intracellular RNA species of two murine coronaviruses: MHV-A59 and MHV-JHM. Virology 114, 39–51.PubMedCrossRefGoogle Scholar
  17. Makino, S., Fujioka, N. and Fujiwara, K. (1985). Structure of the intracellular defective viral RNAs of defective interfering particles of mouse hepatitis virus. J. Virol. 54, 329–336.PubMedGoogle Scholar
  18. Makino, S., Stohlman, S.A., and Lai, M.M.C. (1986). Leader sequences of murine coronavirus mRNAs can be freely reassorted: Evidence for the role of free leader RNA in transcription. Proc. Natl. Acad. Sci. USA 83, 4204–4208.PubMedCrossRefGoogle Scholar
  19. Makino, S., Taguchi, F., and Fujiwara, K. (1984a). Defective interfering particles of mouse hepatitis virus. Virology 133, 9–17.PubMedCrossRefGoogle Scholar
  20. Makino, S., Taguchi, R., Hirano, N., and Fujiwara, K. (1984b). Analysis of genomic and intracellular viral RNAs of small plaque mutants of mouse hepatitis virus, JHM strain. Virology 139, 138–151.PubMedCrossRefGoogle Scholar
  21. Maniatis, T., Fritsch, E.F., and Sambrook, J. (1982). “Molecular Cloning-A Laboratory Manual.” Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.Google Scholar
  22. Mills, D.R., Dabkin, C. and Kramer, F.R. (1978). Template-determined, variable rate of RNA chain elongation. Cell 15, 541–550.PubMedCrossRefGoogle Scholar
  23. Sanger, F., Nicklen, S., and Coulson, A.R. (1977). DNA sequencing with chainterminating inhibitors. Proc. Natl. Acad. Sci. USA 74, 5463–5467.PubMedCrossRefGoogle Scholar
  24. Skinner, M.A., Ebner, D., and Siddell, S.C. (1985). Coronavirus MHV-JHM mRNA 5 has a sequence arrangement which potentially allows translation of a second, downstream open reading frame. J. Gen. Virol. 66, 581–592.PubMedCrossRefGoogle Scholar
  25. Skinner, M.A., and Siddell, S.G. (1983). Coronavirus JHM: Nucleotide sequence of the mRNA that encodes nucleocapsid protein. Nucleic Acids Res. 15, 5045–5054.CrossRefGoogle Scholar
  26. Skinner, M.A., and Siddell, S.G. (1985). Coding sequence of coronavirus MHV-JHM mRNA 4. J. Gen. Virol. 66, 593–596.PubMedCrossRefGoogle Scholar
  27. Spaan, W., Delius, H., Skinner, M., Armstrong, J., Rottier, P., Smeekens, S., Van der Zeijst, B.A.M., and Siddell, S.G. (1983). Coronavirus mRNA synthesis involves fusion of non-contiguous sequences. EMBO J. 2, 1839–1844.PubMedGoogle Scholar
  28. Wilhelmsen, K.C., Leiboweitz, J.L., Bond, C.W., and Robb, J.A. (1981). The replication of murine coronaviruses in enucleated cells. Virology 110, 225–230.PubMedCrossRefGoogle Scholar
  29. Zaret, K.S., and Sherman, F. (1982). DNA sequence required for efficient transcription termination in yeast. Cell 28, 563–573.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Lisa H. Soe
    • 1
  • Chien-Kou Shieh
    • 1
  • Shinji Makino
    • 1
  • Ming-Fu Chang
    • 1
  • Stephen A. Stohlman
    • 1
  • Michael M. C. Lai
    • 1
  1. 1.Departments of Microbiology and NeurologyUniversity of Southern California School of MedicineLos AngelesUSA

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