Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1995 Nov;69(11):7054–7060. doi: 10.1128/jvi.69.11.7054-7060.1995

A transcript from the long terminal repeats of a murine retrovirus associated with trans activation of cellular genes.

S Y Choi 1, D V Faller 1
PMCID: PMC189625  PMID: 7474125

Abstract

Infection of human or murine cells with murine leukemia viruses rapidly increases the expression of a number of genes that belong to the immunoglobulin superfamily and are involved in T-lymphocyte activation, including the class I major histocompatibility complex antigens. We have reported recently that the long terminal repeat (LTR) of Moloney murine leukemia virus encodes a trans activator which induces transcription and expression of class I major histocompatibility complex genes and certain cytokine genes. The portion of the LTR responsible for trans activation was mapped by deletions to lie within the U3 region. We demonstrate here that a transcript is initiated within the U3 region and that its presence correlates with the trans-activating activity. Analysis of the LTR region reveals a potential internal promoter element for RNA polymerase III transcription within the U3 region. Studies with polymerase inhibitors suggest that this LTR transcript, designated let (LTR-encoded trans activator), is a product of RNA polymerase III. The mechanisms whereby RNA leukemia viruses cause lymphoid neoplasia after a long latent period have been extensively studied but are only partially understood. The region of the LTR identified here as being important in trans activation has recently been shown to be a critical determinant of the leukemogenicity and latency of Moloney murine leukemia virus. These findings suggest a novel mechanism of retrovirus-induced activation of cellular gene expression, potentially contributing to leukemogenesis.

Full Text

The Full Text of this article is available as a PDF (414.8 KB).

Selected References

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

  1. Brannan C. I., Dees E. C., Ingram R. S., Tilghman S. M. The product of the H19 gene may function as an RNA. Mol Cell Biol. 1990 Jan;10(1):28–36. doi: 10.1128/mcb.10.1.28. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Braun B. R., Riggs D. L., Kassavetis G. A., Geiduschek E. P. Multiple states of protein-DNA interaction in the assembly of transcription complexes on Saccharomyces cerevisiae 5S ribosomal RNA genes. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2530–2534. doi: 10.1073/pnas.86.8.2530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brightman B. K., Rein A., Trepp D. J., Fan H. An enhancer variant of Moloney murine leukemia virus defective in leukemogenesis does not generate detectable mink cell focus-inducing virus in vivo. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2264–2268. doi: 10.1073/pnas.88.6.2264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brockdorff N., Ashworth A., Kay G. F., McCabe V. M., Norris D. P., Cooper P. J., Swift S., Rastan S. The product of the mouse Xist gene is a 15 kb inactive X-specific transcript containing no conserved ORF and located in the nucleus. Cell. 1992 Oct 30;71(3):515–526. doi: 10.1016/0092-8674(92)90519-i. [DOI] [PubMed] [Google Scholar]
  5. Celander D., Haseltine W. A. Tissue-specific transcription preference as a determinant of cell tropism and leukaemogenic potential of murine retroviruses. Nature. 1984 Nov 8;312(5990):159–162. doi: 10.1038/312159a0. [DOI] [PubMed] [Google Scholar]
  6. Chazan R., Haran-Ghera N. The role of thymus subpopulations in "T" leukemia development. Cell Immunol. 1976 May;23(2):356–375. doi: 10.1016/0008-8749(76)90200-8. [DOI] [PubMed] [Google Scholar]
  7. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  8. Choi S. Y., Faller D. V. The long terminal repeats of a murine retrovirus encode a trans-activator for cellular genes. J Biol Chem. 1994 Aug 5;269(31):19691–19694. [PubMed] [Google Scholar]
  9. Chumakov I., Stuhlmann H., Harbers K., Jaenisch R. Cloning of two genetically transmitted Moloney leukemia proviral genomes: correlation between biological activity of the cloned DNA and viral genome activation in the animal. J Virol. 1982 Jun;42(3):1088–1098. doi: 10.1128/jvi.42.3.1088-1098.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ciliberto G., Raugei G., Costanzo F., Dente L., Cortese R. Common and interchangeable elements in the promoters of genes transcribed by RNA polymerase iii. Cell. 1983 Mar;32(3):725–733. doi: 10.1016/0092-8674(83)90058-2. [DOI] [PubMed] [Google Scholar]
  11. Davis B. R., Brightman B. K., Chandy K. G., Fan H. Characterization of a preleukemic state induced by Moloney murine leukemia virus: evidence for two infection events during leukemogenesis. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4875–4879. doi: 10.1073/pnas.84.14.4875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Davis B., Linney E., Fan H. Suppression of leukaemia virus pathogenicity by polyoma virus enhancers. Nature. 1985 Apr 11;314(6011):550–553. doi: 10.1038/314550a0. [DOI] [PubMed] [Google Scholar]
  13. Flyer D. C., Burakoff S. J., Faller D. V. Expression and CTL recognition of cloned subgenomic fragments of Moloney murine leukemia virus in murine cells. Surv Immunol Res. 1985;4(2):168–172. doi: 10.1007/BF02918812. [DOI] [PubMed] [Google Scholar]
  14. Flyer D. C., Burakoff S. J., Faller D. V. Retrovirus-induced changes in major histocompatibility complex antigen expression influence susceptibility to lysis by cytotoxic T lymphocytes. J Immunol. 1985 Oct;135(4):2287–2292. [PubMed] [Google Scholar]
  15. Gorska-Flipot I., Huang M., Cantin M., Rassart E., Massé G., Jolicoeur P. U3 long terminal repeat-mediated induction of intracellular immunity by a murine retrovirus: a novel model of latency for retroviruses. J Virol. 1992 Dec;66(12):7201–7210. doi: 10.1128/jvi.66.12.7201-7210.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hao Y., Crenshaw T., Moulton T., Newcomb E., Tycko B. Tumour-suppressor activity of H19 RNA. Nature. 1993 Oct 21;365(6448):764–767. doi: 10.1038/365764a0. [DOI] [PubMed] [Google Scholar]
  17. Hassan Y., Priel E., Segal S., Huleihel M., Aboud M. Chemical-retroviral cooperative carcinogenesis and its molecular basis in NIH/3T3 cells. Carcinogenesis. 1990 Dec;11(12):2097–2102. doi: 10.1093/carcin/11.12.2097. [DOI] [PubMed] [Google Scholar]
  18. Henley S. L., Wise K. S., Acton R. T. Productive murine leukemia virus (MuLV) infection of EL4 T-lymphoblastoid cells: selective elevation of H-2 surface expression and possible association of Thy-1 antigen with viruses. Adv Exp Med Biol. 1984;172:365–381. doi: 10.1007/978-1-4615-9376-8_21. [DOI] [PubMed] [Google Scholar]
  19. Kassavetis G. A., Riggs D. L., Negri R., Nguyen L. H., Geiduschek E. P. Transcription factor IIIB generates extended DNA interactions in RNA polymerase III transcription complexes on tRNA genes. Mol Cell Biol. 1989 Jun;9(6):2551–2566. doi: 10.1128/mcb.9.6.2551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kaufman R. J., Davies M. V., Pathak V. K., Hershey J. W. The phosphorylation state of eucaryotic initiation factor 2 alters translational efficiency of specific mRNAs. Mol Cell Biol. 1989 Mar;9(3):946–958. doi: 10.1128/mcb.9.3.946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kimura A., Israël A., Le Bail O., Kourilsky P. Detailed analysis of the mouse H-2Kb promoter: enhancer-like sequences and their role in the regulation of class I gene expression. Cell. 1986 Jan 31;44(2):261–272. doi: 10.1016/0092-8674(86)90760-9. [DOI] [PubMed] [Google Scholar]
  22. Koka P., van de Mark K., Faller D. V. trans-Activation of genes encoding activation-associated human T lymphocyte surface proteins by murine retroviral sequences. J Immunol. 1991 Apr 1;146(7):2417–2425. [PubMed] [Google Scholar]
  23. Larsson S., Bellett A., Akusjärvi G. VA RNAs from avian and human adenoviruses: dramatic differences in length, sequence, and gene location. J Virol. 1986 May;58(2):600–609. doi: 10.1128/jvi.58.2.600-609.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lenz J., Celander D., Crowther R. L., Patarca R., Perkins D. W., Haseltine W. A. Determination of the leukaemogenicity of a murine retrovirus by sequences within the long terminal repeat. 1984 Mar 29-Apr 4Nature. 308(5958):467–470. doi: 10.1038/308467a0. [DOI] [PubMed] [Google Scholar]
  25. Meruelo D., Nimelstein S. H., Jones P. P., Lieberman M., McDevitt H. O. Increased synthesis and expression of H-2 antigens on thymocytes as a result of radiation leukemia virus infection: a possible mechanism for H-2 linked control of virus-induced neoplasia. J Exp Med. 1978 Feb 1;147(2):470–487. doi: 10.1084/jem.147.2.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mundschau L. J., Faller D. V. Platelet-derived growth factor signal transduction through the interferon-inducible kinase PKR. Immediate early gene induction. J Biol Chem. 1995 Feb 17;270(7):3100–3106. doi: 10.1074/jbc.270.7.3100. [DOI] [PubMed] [Google Scholar]
  27. Nielsen J. N., Hallenberg C., Frederiksen S., Sørensen P. D., Lomholt B. Transcription of human 5S rRNA genes is influenced by an upstream DNA sequence. Nucleic Acids Res. 1993 Aug 11;21(16):3631–3636. doi: 10.1093/nar/21.16.3631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Oprian D. D., Molday R. S., Kaufman R. J., Khorana H. G. Expression of a synthetic bovine rhodopsin gene in monkey kidney cells. Proc Natl Acad Sci U S A. 1987 Dec;84(24):8874–8878. doi: 10.1073/pnas.84.24.8874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Petrarca M. A., Reiss C. S., Diamond D. C., Boni J., Burakoff S. J., Faller D. V. T cell hybridomas define the class II MHC-restricted response to vesicular stomatitis virus infection. Microb Pathog. 1988 Nov;5(5):319–332. doi: 10.1016/0882-4010(88)90033-2. [DOI] [PubMed] [Google Scholar]
  30. Rastinejad F., Blau H. M. Genetic complementation reveals a novel regulatory role for 3' untranslated regions in growth and differentiation. Cell. 1993 Mar 26;72(6):903–917. doi: 10.1016/0092-8674(93)90579-f. [DOI] [PubMed] [Google Scholar]
  31. Renfranz P. J., Cunningham M. G., McKay R. D. Region-specific differentiation of the hippocampal stem cell line HiB5 upon implantation into the developing mammalian brain. Cell. 1991 Aug 23;66(4):713–729. doi: 10.1016/0092-8674(91)90116-g. [DOI] [PubMed] [Google Scholar]
  32. Sinnett D., Richer C., Deragon J. M., Labuda D. Alu RNA secondary structure consists of two independent 7 SL RNA-like folding units. J Biol Chem. 1991 May 15;266(14):8675–8678. [PubMed] [Google Scholar]
  33. Sodroski J. G., Rosen C. A., Haseltine W. A. Trans-acting transcriptional activation of the long terminal repeat of human T lymphotropic viruses in infected cells. Science. 1984 Jul 27;225(4660):381–385. doi: 10.1126/science.6330891. [DOI] [PubMed] [Google Scholar]
  34. Sodroski J., Rosen C., Wong-Staal F., Salahuddin S. Z., Popovic M., Arya S., Gallo R. C., Haseltine W. A. Trans-acting transcriptional regulation of human T-cell leukemia virus type III long terminal repeat. Science. 1985 Jan 11;227(4683):171–173. doi: 10.1126/science.2981427. [DOI] [PubMed] [Google Scholar]
  35. Speck N. A., Renjifo B., Golemis E., Fredrickson T. N., Hartley J. W., Hopkins N. Mutation of the core or adjacent LVb elements of the Moloney murine leukemia virus enhancer alters disease specificity. Genes Dev. 1990 Feb;4(2):233–242. doi: 10.1101/gad.4.2.233. [DOI] [PubMed] [Google Scholar]
  36. Steinberg T. H., Mathews D. E., Durbin R. D., Burgess R. R. Tagetitoxin: a new inhibitor of eukaryotic transcription by RNA polymerase III. J Biol Chem. 1990 Jan 5;265(1):499–505. [PubMed] [Google Scholar]
  37. Varmus H. Regulation of HIV and HTLV gene expression. Genes Dev. 1988 Sep;2(9):1055–1062. doi: 10.1101/gad.2.9.1055. [DOI] [PubMed] [Google Scholar]
  38. Weil P. A., Segall J., Harris B., Ng S. Y., Roeder R. G. Faithful transcription of eukaryotic genes by RNA polymerase III in systems reconstituted with purified DNA templates. J Biol Chem. 1979 Jul 10;254(13):6163–6173. [PubMed] [Google Scholar]
  39. Weng H., Choi S. Y., Faller D. V. The Moloney leukemia retroviral long terminal repeat trans-activates AP-1-inducible genes and AP-1 transcription factor binding. J Biol Chem. 1995 Jun 9;270(23):13637–13644. doi: 10.1074/jbc.270.23.13637. [DOI] [PubMed] [Google Scholar]
  40. Wilson L. D., Flyer D. C., Faller D. V. Murine retroviruses control class I major histocompatibility antigen gene expression via a trans effect at the transcriptional level. Mol Cell Biol. 1987 Jul;7(7):2406–2415. doi: 10.1128/mcb.7.7.2406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wolffe A. P., Brown D. D. Developmental regulation of two 5S ribosomal RNA genes. Science. 1988 Sep 23;241(4873):1626–1632. doi: 10.1126/science.241.4873.1626. [DOI] [PubMed] [Google Scholar]

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

RESOURCES