Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1983 Sep;47(3):495–504. doi: 10.1128/jvi.47.3.495-504.1983

Nucleotide sequencing of an apparent proviral copy of env mRNA defines determinants of expression of the mouse mammary tumor virus env gene.

J E Majors, H E Varmus
PMCID: PMC255291  PMID: 6312081

Abstract

To extend our understanding of the organization and expression of the mouse mammary tumor virus genome, we determined the nucleotide sequence of large regions of a cloned mouse mammary tumor virus strain C3H provirus that appears to be a DNA copy of env mRNA. In conjunction with analysis of several additional clones of integrated and unintegrated mouse mammary tumor virus DNAs, we came to the following conclusions: (i) the mRNA for env is generated by splicing mechanisms that recognize conventional eucaryotic signals at donor and acceptor sites with a leader of at least 289 bases in length; (ii) the first of three possible initiation codons for translation of env follows the splice junction by a single nucleotide and produces a signal peptide of 98 amino acids; (iii) the amino terminal sequence of the major virion glycoprotein gp52env is confirmed by nucleotide sequencing and is encoded by a sequence beginning 584 nucleotides from the 5' end of env mRNA; (iv) the final 17 amino acids at the carboxyl terminus of the primary product of env are encoded within the long terminal repeat by the 51 bases at the 5' end of the U3 domain; and (v) bases 2 through 4 at the 5' end of the long terminal repeat constitute an initiation codon that commences an open reading frame capable of directing the synthesis of a 36-kilodalton protein.

Full text

PDF
495

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arthur L. O., Altrock B. W., Schochetman G. Type-specific determinants on proteins of an endogenous C3H mouse mammary tumor virus (MMTV) distinguish this virus from highly oncogenic exogenous MMTVs. Virology. 1981 Apr 30;110(2):270–280. doi: 10.1016/0042-6822(81)90059-3. [DOI] [PubMed] [Google Scholar]
  2. Arthur L. O., Copeland T. D., Oroszlan S., Schochetman G. Processing and amino acid sequence analysis of the mouse mammary tumor virus env gene product. J Virol. 1982 Feb;41(2):414–422. doi: 10.1128/jvi.41.2.414-422.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dickson C., Atterwill M. Structure and processing of the mouse mammary tumor virus glycoprotein precursor pr73env. J Virol. 1980 Aug;35(2):349–361. doi: 10.1128/jvi.35.2.349-361.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dickson C., Peters G. Protein-coding potential of mouse mammary tumor virus genome RNA as examined by in vitro translation. J Virol. 1981 Jan;37(1):36–47. doi: 10.1128/jvi.37.1.36-47.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dickson C., Smith R., Peters G. In vitro synthesis of polypeptides encoded by the long terminal repeat region of mouse mammary tumour virus DNA. Nature. 1981 Jun 11;291(5815):511–513. doi: 10.1038/291511a0. [DOI] [PubMed] [Google Scholar]
  6. Donehower L. A., Fleurdelys B., Hager G. L. Further evidence for the protein coding potential of the mouse mammary tumor virus long terminal repeat: nucleotide sequence of an endogenous proviral long terminal repeat. J Virol. 1983 Mar;45(3):941–949. doi: 10.1128/jvi.45.3.941-949.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Donehower L. A., Huang A. L., Hager G. L. Regulatory and coding potential of the mouse mammary tumor virus long terminal redundancy. J Virol. 1981 Jan;37(1):226–238. doi: 10.1128/jvi.37.1.226-238.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dudley J. P., Varmus H. E. Purification and translation of murine mammary tumor virus mRNA's. J Virol. 1981 Jul;39(1):207–218. doi: 10.1128/jvi.39.1.207-218.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Emr S. D., Silhavy T. J. Molecular components of the signal sequence that function in the initiation of protein export. J Cell Biol. 1982 Dec;95(3):689–696. doi: 10.1083/jcb.95.3.689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fasel N., Pearson K., Buetti E., Diggelmann H. The region of mouse mammary tumor virus DNA containing the long terminal repeat includes a long coding sequence and signals for hormonally regulated transcription. EMBO J. 1982;1(1):3–7. doi: 10.1002/j.1460-2075.1982.tb01115.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hackett P. B., Swanstrom R., Varmus H. E., Bishop J. M. The leader sequence of the subgenomic mRNA's of Rous sarcoma virus is approximately 390 nucleotides. J Virol. 1982 Feb;41(2):527–534. doi: 10.1128/jvi.41.2.527-534.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kennedy N., Knedlitschek G., Groner B., Hynes N. E., Herrlich P., Michalides R., van Ooyen A. J. Long terminal repeats of endogenous mouse mammary tumour virus contain a long open reading frame which extends into adjacent sequences. Nature. 1982 Feb 18;295(5850):622–624. doi: 10.1038/295622a0. [DOI] [PubMed] [Google Scholar]
  13. Klemenz R., Reinhardt M., Diggelmann H. Sequence determination of the 3' end of mouse mammary tumor virus RNA. Mol Biol Rep. 1981 May 22;7(1-3):123–126. doi: 10.1007/BF00778742. [DOI] [PubMed] [Google Scholar]
  14. Kozak M. Possible role of flanking nucleotides in recognition of the AUG initiator codon by eukaryotic ribosomes. Nucleic Acids Res. 1981 Oct 24;9(20):5233–5252. doi: 10.1093/nar/9.20.5233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Majors J. E., Varmus H. E. Nucleotide sequences at host-proviral junctions for mouse mammary tumour virus. Nature. 1981 Jan 22;289(5795):253–258. doi: 10.1038/289253a0. [DOI] [PubMed] [Google Scholar]
  16. Maxam A. M., Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. doi: 10.1073/pnas.74.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mount S. M. A catalogue of splice junction sequences. Nucleic Acids Res. 1982 Jan 22;10(2):459–472. doi: 10.1093/nar/10.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Redmond S. M., Dickson C. Sequence and expression of the mouse mammary tumour virus env gene. EMBO J. 1983;2(1):125–131. doi: 10.1002/j.1460-2075.1983.tb01393.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ringold G. M., Yamamoto K. R., Bishop J. M., Varmus H. E. Glucocorticoid-stimulated accumulation of mouse mammary tumor virus RNA: increased rate of synthesis of viral RNA. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2879–2883. doi: 10.1073/pnas.74.7.2879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Shinnick T. M., Lerner R. A., Sutcliffe J. G. Nucleotide sequence of Moloney murine leukaemia virus. Nature. 1981 Oct 15;293(5833):543–548. doi: 10.1038/293543a0. [DOI] [PubMed] [Google Scholar]
  21. Stacey D. W. Expression of a subgenomic retroviral messenger RNA. Cell. 1980 Oct;21(3):811–820. doi: 10.1016/0092-8674(80)90444-4. [DOI] [PubMed] [Google Scholar]
  22. Swanstrom R., Varmus H. E., Bishop J. M. Nucleotide sequence of the 5' noncoding region and part of the gag gene of Rous sarcoma virus. J Virol. 1982 Feb;41(2):535–541. doi: 10.1128/jvi.41.2.535-541.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Takanami M. RNA polymerase nascent product analysis. Methods Enzymol. 1980;65(1):497–499. doi: 10.1016/s0076-6879(80)65058-7. [DOI] [PubMed] [Google Scholar]
  24. Wheeler D. A., Butel J. S., Medina D., Cardiff R. D., Hager G. L. Transcription of mouse mammary tumor virus: identification of a candidate mRNA for the long terminal repeat gene product. J Virol. 1983 Apr;46(1):42–49. doi: 10.1128/jvi.46.1.42-49.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Young H. A., Shih T. Y., Scolnick E. M., Parks W. P. Steroid induction of mouse mammary tumor virus: effect upon synthesis and degradation of viral RNA. J Virol. 1977 Jan;21(1):139–146. doi: 10.1128/jvi.21.1.139-146.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. van Ooyen A. J., Michalides R. J., Nusse R. Structural analysis of a 1.7-kilobase mouse mammary tumor virus-specific RNA. J Virol. 1983 May;46(2):362–370. doi: 10.1128/jvi.46.2.362-370.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES