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Volume 77, Issue 5

Expression of novel transposon-containing mRNAs in human T cells Free

Abstract

The HERV-H family of endogenous retrovirus like elements is the largest such human family known. Using an HERV-H LTR probe, 6 and 4.5 kb transcripts were detected by Northern blot analysis which were induced in normal peripheral T cells after treatment with phytohaemaglutinin (PHA). Expression was not evident 30 min after treatment with phorbol ester, was increased within 3–4 h after treatment, reached a maximum after 8 h and then declined to low levels 24 h after treatment. Expression was inhibited totally by cycloheximide (10 µ) and by the immunosuppressant cyclosporin A (1 µg/ml). Using probes specific for the U3 and U5 regions of the HERV-H LTR, in combination with internal HERV-H probes, evidence was obtained that the 6 and 4.5 kb transcripts are polyadenylated from an HERV-H LTR. A cDNA library was constructed from T cells which had been treated with PHA for 8 h and a 1.7 kb clone was isolated using the HERV-H LTR probe. The insert contained a novel tandem array of an Alu, a LINE-1 element, two endogenous retroviral LTRs and an A-T-rich sequence. The A-T-rich sequence contained multiple copies of AUUUA mRNA regulatory motifs. Because of its high expression level, defined transcription kinetics, novel cassette-like composition and the presence of conserved mRNA stabilization sequences, we hypothesize that the transcript may play a biological role during T cell activation.

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© Journal of General Virology 1996
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1996-05-01
2024-04-19
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References

  1. Abraham G. N., Khan A. S. 1990; Human endogenous retroviruses in immune disease. Clinical Immunology and Immunopathology 56:1–8
     [Google Scholar]
  2. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. 1990; Basic local alignment search tool. Journal of Molecular Biology 215:403–410
     [Google Scholar]
  3. Andrews P. W., Damjanov I., Simon D., Banting G. S., Carlin C., Dracopoli N. C., Fogh J. 1984; Pluripotent embryonal carcinoma clones derived from human teratocarcinoma cell line Tera-2. Laboratory Investigation 50:147–162
     [Google Scholar]
  4. Boeke J. D., Garfinkel D. J., Styles C. A., Fink G. R. 1985; Ty elements transpose through an RNA intermediate. Cell 40:491–500
     [Google Scholar]
  5. Brodsky I., Foley B., Haines D., Johnston J., Cuddy K., Gillespie D. 1993; Expression of HERV-K proviruses in human leukoctyes. Blood 81:2369–2374
     [Google Scholar]
  6. Ciampolillo A., Mirakian R., Schultz T., Marini V., Buscema M., Pujol-Borrell R., Franco Bottazzo G. 1989; Retroviruslike sequences in Graves’ disease: implications for human autoimmunity. Lancet (May 20) 1096–1099
     [Google Scholar]
  7. Crabtree G. R. 1989; Contingent genetic regulatory events in T lymphocyte activation. Science 243:355–361
     [Google Scholar]
  8. Davis L. G., Dibner M. D., Battey J. F. 1986 Basic Methods in Molecular Biology New York: Elsevier Science Publishing;
     [Google Scholar]
  9. Deininger P. L. 1989; SINES: short interspersed repeat DNA elements in higher eukaryotes. In Mobile DNA pp 619–636 Edited by Berg D. E., Howe M. M. Washington, DC: American Society for Microbiology;
     [Google Scholar]
  10. Devereux J., Haeberli P., Smithies O. 1984; A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Research 12:387–395
     [Google Scholar]
  11. Dombroski B. A., Mathias S. L., Nanthakunar E., Scott A. F., Kazazian H. H. 1991; Isolation of a human transposable element. Science 254:1805–1808
     [Google Scholar]
  12. Fanning T., Singer M. 1987; The LINE-1 DNA sequences in four mammalian orders predict proteins that conserve homologies to retroviral particles. Nucleic Acids Research 15:2251–2260
     [Google Scholar]
  13. Feuchter-Murthy A., Freeman J. D., Mager D. L. 1992; Strategy for detecting cellular transcripts promoted by human long terminal repeats: identification of a novel gene (CDC 4L) with homology to yeast CDC 4. Genomics 13:1237–1246
     [Google Scholar]
  14. Garry R. F., Fermin C., Hart D., Alexander S., Donehower L. A., Luo-Zhang H. 1990; Detection of a human intracisternal A-type particle antigenically related to HIV. Science 250:1127–1129
     [Google Scholar]
  15. Gillis S., Watson J. 1980; Biochemical and biological characterisation of lymphocyte regulatory molecules. Journal of Experimental Medicine 152:1709–1719
     [Google Scholar]
  16. Goodchild N. L., Wilkinson D. A., Mager D. L. 1992; A human endogenous long terminal repeat provides a polyadenylation signal to a novel, alternatively spliced transcript in normal placenta. Gene 121:287–294
     [Google Scholar]
  17. Hirose Y., Takamatsu M., Harada F. 1993; Presence of env genes in members of the RTVL-H family of human endogenous retrovirus like elements. Virology 192:52–61
     [Google Scholar]
  18. Johansen T., Holm T., Bjorklid E. 1989; Members of the RTVL-H family of human endogenous retrovirus-like elements are expressed in placenta. Gene 79:259–267
     [Google Scholar]
  19. Kazazian H. H., Wong C., Youssouffian H., Scott A. F., Phillips D. G., Antonirakis S. E. 1988; Haemophilia A resulting from de novo insertion of LI reveals a novel mechanism for mutation in man. Nature 332:164–166
     [Google Scholar]
  20. Kelleher C. A., Wilkinson D. A., Mager D. L. 1990; Abnormal expression of a novel transcript polyadenylated by a human endogenous long terminal repeat (LTR) in primary human leukemic marrow and blood cells. Blood 76:234a
     [Google Scholar]
  21. Krieg A., Gourley M. F., Klinman D. M., Perl A., Steinberg A. D. 1992; Heterogeneous expression and coordinate regulation of endogenous retroviral sequences in human peripheral blood mononuclear cells. AIDS Research and Human Retroviruses 8:1991–1998
     [Google Scholar]
  22. Kumagai N., Benedict S. H., Mills G. B., Gelfand E. W. 1988; Comparison of phorbol ester/calcium ionophore and phytohemagglutinin-induced signalling in human T lymphocytes. Demonstration of interleukin 2-independent transferrin receptor gene expression. Journal of Immunology 140:37–43
     [Google Scholar]
  23. Kurth R. 1986; Endogenous retrovirus in multiple sclerosis?. Nature 320:219–220
     [Google Scholar]
  24. Liu A. Y., Abraham B. A. 1991; Subtractive cloning of a hybrid human endogenous retrovirus and calbindin gene in the prostate cell line PC3. Cancer Research 51:4107–4110
     [Google Scholar]
  25. Mager D. L. 1989; Polyadenylation function and sequence variability of the long terminal repeats of the human endogenous retrovirus-like family RTVL-H. Virology 173:591–599
     [Google Scholar]
  26. Mager D. L., Henthorn P. S. 1984; Identification of a retroviruslike repetitive element in human DNA. Proceedings of the National Academy of Sciences, USA 81:7510–7514
     [Google Scholar]
  27. Mager D. L., Freeman J. D. 1987; Human endogenous retroviruslike genome with type C pol sequences and gag sequences related to human T cell lymphotropic viruses. Journal of Virology 61:4060–4066
     [Google Scholar]
  28. Martin M. A., Bryan T., Rasheed S., Khan A. S. 1981; Identification and cloning of endogenous retroviral sequences present in human DNA. Proceedings of the National Academy of Sciences, USA 78:4892–4896
     [Google Scholar]
  29. Medstand P., Lindeskog M., Blomberg J. 1992; Expression of human endogenous retroviral sequences in peripheral blood mononuclear cells of healthy individuals. Journal of General Virology 73:2463–2466
     [Google Scholar]
  30. Miki Y., Nishisho L., Horii A., Miyoshi Y., Utsunomiya J., Kinzler K. W., Vogelstein B., Nakamura Y. 1992; Disruption of the APC gene by retrotransposal insertion of LI sequence in a colon cancer. Cancer Research 52:643–645
     [Google Scholar]
  31. Morse B., Rothberg P. G., South V. J., Spandorfer J. M., Astrin S. M. 1988; Insertional mutagenesis of the myc locus by a LINE-1 sequence in a human breast carcinoma. Nature 333:87–90
     [Google Scholar]
  32. Muranyi W., Darai G., Flugel R. M. 1988; Nucleotide sequence of a human retrotransposon region encoding a reverse transcriptaselike protein. Nucleic Acids Research 16:7724–7729
     [Google Scholar]
  33. Nagarajan L., Lange B., Cannizaro L., Finan J., Nowell P. C., Huebner K. 1990; Molecular anatomy of a 5q interstitial deletion. Blood 75:82–87
     [Google Scholar]
  34. Nimer S. D., Golds D. W. 1987; The 5q-abnormality. Blood 70:1705–1712
     [Google Scholar]
  35. Or R., Renz H., Terada N., Gelfand E. W. 1992; IL-4 and IL-2 promote human T cell proliferation through symmetrical but independent pathways. Clinical Immunology and Immunopathology 64:210–217
     [Google Scholar]
  36. Peltz S. W., Brewer G., Bernstein P., Hart P. A., Ross J. 1991; Regulation of mRNA turnover in eukaryotic cells. Critical Reviews in Eukaryotic Gene Expression 1:99–126
     [Google Scholar]
  37. Schreiber S. 1992; Immunophilin-sensitive protein-phosphatase action in cell signalling pathways. Cell 70:365–368
     [Google Scholar]
  38. Shaw G., Kamen R. 1986; A conserved AU sequence from the 3′ untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell 46:659–667
     [Google Scholar]
  39. Tabor S., Richardson C. C. 1987; DNA sequence analysis with a modified bacteriophage T7 DNA polymerase. Proceedings of the National Academy of Sciences, USA 84:4767–4771
     [Google Scholar]
  40. Terada N., Or R., Weinberg K., Domenico J., Lucas J. J., Gelfand E. W. 1992; Transcription of IL-2 and ILA genes is not inhibited by cyclosporin A in competent T cells. Journal of Biological Chemistry 267:21207–21210
     [Google Scholar]
  41. Vidaud D., Vidaud M., Bahnak B. R., Siguret V., Sanchez S. G., Laurian Y., Meyer D., Goossens M., Lavergne J. M. 1993; Haemophilia B due to a de novo insertion of a human specific Alu subfamily member within the coding region of the factor IX gene. European Journal of Human Genetics 1:30–36
     [Google Scholar]
  42. Wallace M. R., Anderson L. B., Saulino A. M., Gregory P. E., Glover T. W., Collins F. S. 1991; A de novo Alu insertion results in neurofibromatosis type 1. Nature 353:864–866
     [Google Scholar]
  43. Weiner A. M., Deininger P. L., Efstratiadis A. 1986; Nonviral retroposons: genes, pseudogenes, and transposable elements generated by the reverse flow of genetic information. Annual Review of Biochemistry 55:631–661
     [Google Scholar]
  44. Wilkinson D. A., Freeman J. D., Goodchild N. L., Kelleher C. A., Mager D. L. 1990; Autonomous expression of RTVL-H endogenous retroviruslike elements in human cells. Journal of Virology 64:2157–2167
     [Google Scholar]
  45. Wilkinson D. A., Mager D. L., Leong J. C. 1994; Endogenous human retroviruses. In The Retroviridae pp 465–535 Edited by Levy J. A. New York: Plenum Press;
     [Google Scholar]
  46. Zipfel P. F., Irving S. G., Kelly K., Siebenlist U. 1989; Complexity of the primary genetic response to mitogenic activation of human T cells. Molecular and Cellular Biology 9:1041–1048
     [Google Scholar]
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Expression of novel transposon-containing mRNAs in human T cells
J. Gen. Virol. 77, 1101 (1996); https://doi.org/10.1099/0022-1317-77-5-1101
/content/journal/jgv/10.1099/0022-1317-77-5-1101
/content/journal/jgv/10.1099/0022-1317-77-5-1101
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