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. 1984 Nov;81(22):6919–6923. doi: 10.1073/pnas.81.22.6919

Regulation of polyomavirus transcription by large tumor antigen.

W G Farmerie, W R Folk
PMCID: PMC392047  PMID: 6095261

Abstract

We have analyzed the regulation of viral transcription by the large tumor antigen in cells infected by several viable deletion and insertion mutants of polyomavirus. We find that deletion of the early promoter "TATA box" and associated large tumor antigen binding site has only a small effect on the balance of early and late mRNAs. Furthermore, transcription of a polyomavirus containing a heterologous adenovirus promoter in place of the normal TATA box and cap sites is regulated by the large tumor antigen. We conclude that repression of polyomavirus early transcription cannot occur simply by binding of the large tumor antigen to DNA sequences at the site of transcription initiation and must involve the interaction of the large tumor antigen binding at other sites.

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Selected References

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

  1. Acheson N. H., Buetti E., Scherrer K., Weil R. Transcription of the polyoma virus genome: synthesis and cleavage of giant late polyoma-specific RNA. Proc Natl Acad Sci U S A. 1971 Sep;68(9):2231–2235. doi: 10.1073/pnas.68.9.2231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Acheson N. H. Polyoma virus giant RNAs contain tandem repeats of the nucleotide sequence of the entire viral genome. Proc Natl Acad Sci U S A. 1978 Oct;75(10):4754–4758. doi: 10.1073/pnas.75.10.4754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Alwine J. C., Khoury G. Effect of a tsA mutation of simian virus 40 late gene expression: variations between host cell lines. J Virol. 1980 Feb;33(2):920–925. doi: 10.1128/jvi.33.2.920-925.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Backman K., Ptashne M. Maximizing gene expression on a plasmid using recombination in vitro. Cell. 1978 Jan;13(1):65–71. doi: 10.1016/0092-8674(78)90138-1. [DOI] [PubMed] [Google Scholar]
  5. Bendig M. M., Folk W. R. Deletion mutants of polyoma virus defining a nonessential region between the origin of replication and the initiation codon for early proteins. J Virol. 1979 Nov;32(2):530–535. doi: 10.1128/jvi.32.2.530-535.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bendig M. M., Folk W. R., Gibson W. Polyoma viruses with mutations at endonuclease HindII site 1: alterations at the COOH terminus of VP1. J Virol. 1979 May;30(2):515–522. doi: 10.1128/jvi.30.2.515-522.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bendig M. M., Thomas T., Folk W. R. Regulatory mutants of polyoma virus defective in DNA replication and the synthesis of early proteins. Cell. 1980 Jun;20(2):401–409. doi: 10.1016/0092-8674(80)90626-1. [DOI] [PubMed] [Google Scholar]
  8. Birg F., Favaloro J., Kamen R. Analysis of polyoma virus nuclear RNA by mini-blot hybridization. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3138–3142. doi: 10.1073/pnas.74.8.3138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Brady J., Bolen J. B., Radonovich M., Salzman N., Khoury G. Stimulation of simian virus 40 late gene expression by simian virus 40 tumor antigen. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2040–2044. doi: 10.1073/pnas.81.7.2040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cogen B. Virus-specific early RNA in 3T6 cells infected by a tsA mutant of polyoma virus. Virology. 1978 Mar;85(1):222–230. doi: 10.1016/0042-6822(78)90426-9. [DOI] [PubMed] [Google Scholar]
  11. Davison B. L., Egly J. M., Mulvihill E. R., Chambon P. Formation of stable preinitiation complexes between eukaryotic class B transcription factors and promoter sequences. Nature. 1983 Feb 24;301(5902):680–686. doi: 10.1038/301680a0. [DOI] [PubMed] [Google Scholar]
  12. DiMaio D., Nathans D. Regulatory mutants of simian virus 40. Effect of mutations at a T antigen binding site on DNA replication and expression of viral genes. J Mol Biol. 1982 Apr 15;156(3):531–548. doi: 10.1016/0022-2836(82)90265-0. [DOI] [PubMed] [Google Scholar]
  13. Dilworth S. M., Cowie A., Kamen R. I., Griffin B. E. DNA binding activity of polyoma virus large tumor antigen. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1941–1945. doi: 10.1073/pnas.81.7.1941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dynan W. S., Tjian R. Isolation of transcription factors that discriminate between different promoters recognized by RNA polymerase II. Cell. 1983 Mar;32(3):669–680. doi: 10.1016/0092-8674(83)90053-3. [DOI] [PubMed] [Google Scholar]
  15. Dynan W. S., Tjian R. The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter. Cell. 1983 Nov;35(1):79–87. doi: 10.1016/0092-8674(83)90210-6. [DOI] [PubMed] [Google Scholar]
  16. Eckhart W. Complementation and transformation by temperature-sensitive mutants of polyoma virus. Virology. 1969 May;38(1):120–125. doi: 10.1016/0042-6822(69)90133-0. [DOI] [PubMed] [Google Scholar]
  17. Fenton R. G., Basilico C. Regulation of polyoma virus early transcription in transformed cells by large T-antigen. Virology. 1982 Sep;121(2):384–392. doi: 10.1016/0042-6822(82)90176-3. [DOI] [PubMed] [Google Scholar]
  18. Flavell A. J., Kamen R. Strand-specific transcription of polyoma virus DNA late during productive infection. J Mol Biol. 1977 Sep 15;115(2):237–242. doi: 10.1016/0022-2836(77)90099-7. [DOI] [PubMed] [Google Scholar]
  19. Folk W. R. Induction of virus synthesis in polyoma-transformed BHK-21 cells. J Virol. 1973 Mar;11(3):424–431. doi: 10.1128/jvi.11.3.424-431.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Fromm M., Berg P. Transcription in vivo from SV40 early promoter deletion mutants without repression by large T antigen. J Mol Appl Genet. 1983;2(1):127–135. [PubMed] [Google Scholar]
  21. Garber E. A., Seidman M. M., Levine A. J. The detection and characterization of multiple forms of SV40 nucleoprotein complexes. Virology. 1978 Oct 15;90(2):305–316. doi: 10.1016/0042-6822(78)90315-x. [DOI] [PubMed] [Google Scholar]
  22. Gaudray P., Tyndall C., Kamen R., Cuzin F. The high affinity binding site on polyoma virus DNA for the viral large-T protein. Nucleic Acids Res. 1981 Nov 11;9(21):5697–5710. doi: 10.1093/nar/9.21.5697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hansen U., Tenen D. G., Livingston D. M., Sharp P. A. T antigen repression of SV40 early transcription from two promoters. Cell. 1981 Dec;27(3 Pt 2):603–613. doi: 10.1016/0092-8674(81)90402-5. [DOI] [PubMed] [Google Scholar]
  24. Heiser W. C., Eckhart W. Polyoma virus early and late mRNAs in productively infected mouse 3T6 cells. J Virol. 1982 Oct;44(1):175–188. doi: 10.1128/jvi.44.1.175-188.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Jat P., Novak U., Cowie A., Tyndall C., Kamen R. DNA sequences required for specific and efficient initiation of transcription at the polyoma virus early promoter. Mol Cell Biol. 1982 Jul;2(7):737–751. doi: 10.1128/mcb.2.7.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kamen R., Jat P., Treisman R., Favaloro J., Folk W. R. 5' termini of polyoma virus early region transcripts synthesized in vivo by wild-type virus and viable deletion mutants. J Mol Biol. 1982 Aug 5;159(2):189–224. doi: 10.1016/0022-2836(82)90493-4. [DOI] [PubMed] [Google Scholar]
  27. Kamen R., Lindstrom D. M., Shure H., Old R. W. Virus-specific RNA in cells productively infected or transformed by polyoma virus. Cold Spring Harb Symp Quant Biol. 1975;39(Pt 1):187–198. doi: 10.1101/sqb.1974.039.01.025. [DOI] [PubMed] [Google Scholar]
  28. Keller J. M., Alwine J. C. Activation of the SV40 late promoter: direct effects of T antigen in the absence of viral DNA replication. Cell. 1984 Feb;36(2):381–389. doi: 10.1016/0092-8674(84)90231-9. [DOI] [PubMed] [Google Scholar]
  29. Myers R. M., Rio D. C., Robbins A. K., Tjian R. SV40 gene expression is modulated by the cooperative binding of T antigen to DNA. Cell. 1981 Aug;25(2):373–384. doi: 10.1016/0092-8674(81)90056-8. [DOI] [PubMed] [Google Scholar]
  30. Parker B. A., Stark G. R. Regulation of simian virus 40 transcription: sensitive analysis of the RNA species present early in infections by virus or viral DNA. J Virol. 1979 Aug;31(2):360–369. doi: 10.1128/jvi.31.2.360-369.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pomerantz B. J., Hassell J. A. Polyomavirus and simian virus 40 large T antigens bind to common DNA sequences. J Virol. 1984 Mar;49(3):925–937. doi: 10.1128/jvi.49.3.925-937.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Pomerantz B. J., Mueller C. R., Hassell J. A. Polyomavirus large T antigen binds independently to multiple, unique regions on the viral genome. J Virol. 1983 Sep;47(3):600–610. doi: 10.1128/jvi.47.3.600-610.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rio D. C., Tjian R. SV40 T antigen binding site mutations that affect autoregulation. Cell. 1983 Apr;32(4):1227–1240. doi: 10.1016/0092-8674(83)90305-7. [DOI] [PubMed] [Google Scholar]
  34. Rio D., Robbins A., Myers R., Tjian R. Regulation of simian virus 40 early transcription in vitro by a purified tumor antigen. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5706–5710. doi: 10.1073/pnas.77.10.5706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Shalloway D., Kleinberger T., Livingston D. M. Mapping of SV40 DNA replication origin region binding sites for the SV40 T antigen by protection against exonuclease III digestion. Cell. 1980 Jun;20(2):411–422. doi: 10.1016/0092-8674(80)90627-3. [DOI] [PubMed] [Google Scholar]
  36. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  37. Tegtmeyer P., Andersen B., Shaw S. B., Wilson V. G. Alternative interactions of the SV40 A protein with DNA. Virology. 1981 Nov;115(1):75–87. doi: 10.1016/0042-6822(81)90090-8. [DOI] [PubMed] [Google Scholar]
  38. Thomas T., Vollmer P., Folk W. R. Nucleotide sequence changes in polyoma virus A gene mutants. J Virol. 1981 Mar;37(3):1094–1098. doi: 10.1128/jvi.37.3.1094-1098.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Tjian R. Protein-DNA interactions at the origin of simian virus 40 DNA replication. Cold Spring Harb Symp Quant Biol. 1979;43(Pt 2):655–661. doi: 10.1101/sqb.1979.043.01.073. [DOI] [PubMed] [Google Scholar]
  40. Tjian R. The binding site on SV40 DNA for a T antigen-related protein. Cell. 1978 Jan;13(1):165–179. doi: 10.1016/0092-8674(78)90147-2. [DOI] [PubMed] [Google Scholar]
  41. Triezenberg S. J., Folk W. R. Essential nucleotides in the polyomavirus origin region. J Virol. 1984 Aug;51(2):437–444. doi: 10.1128/jvi.51.2.437-444.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Tyndall C., La Mantia G., Thacker C. M., Favaloro J., Kamen R. A region of the polyoma virus genome between the replication origin and late protein coding sequences is required in cis for both early gene expression and viral DNA replication. Nucleic Acids Res. 1981 Dec 11;9(23):6231–6250. doi: 10.1093/nar/9.23.6231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Weil P. A., Luse D. S., Segall J., Roeder R. G. Selective and accurate initiation of transcription at the Ad2 major late promotor in a soluble system dependent on purified RNA polymerase II and DNA. Cell. 1979 Oct;18(2):469–484. doi: 10.1016/0092-8674(79)90065-5. [DOI] [PubMed] [Google Scholar]
  44. Weil R., Salomon E., May E., May P. A simplifying concept in tumor virology: virus-specific "pleiotropic effectors". Cold Spring Harb Symp Quant Biol. 1975;39(Pt 1):381–395. doi: 10.1101/sqb.1974.039.01.050. [DOI] [PubMed] [Google Scholar]
  45. Ziff E. B., Evans R. M. Coincidence of the promoter and capped 5' terminus of RNA from the adenovirus 2 major late transcription unit. Cell. 1978 Dec;15(4):1463–1475. doi: 10.1016/0092-8674(78)90070-3. [DOI] [PubMed] [Google Scholar]
  46. de Villiers J., Schaffner W. A small segment of polyoma virus DNA enhances the expression of a cloned beta-globin gene over a distance of 1400 base pairs. Nucleic Acids Res. 1981 Dec 11;9(23):6251–6264. doi: 10.1093/nar/9.23.6251. [DOI] [PMC free article] [PubMed] [Google Scholar]

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