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. 1987 Jul;84(14):5038–5042. doi: 10.1073/pnas.84.14.5038

Interferon messenger RNA is produced constitutively in the organs of normal individuals.

M G Tovey, M Streuli, I Gresser, J Gugenheim, B Blanchard, J Guymarho, F Vignaux, M Gigou
PMCID: PMC305242  PMID: 3110782

Abstract

The use of RNA blot hybridization with DNA or RNA probes of high specific activity has shown that interferon (IFN)-alpha mRNA is present constitutively in the spleen, kidney, liver, and peripheral blood leukocytes of normal individuals. A single band (approximately equal to 1.2 kilobases) was detected in poly(A)+ RNA isolated from human organs. This RNA hybridized specifically to human IFN-alpha 1 DNA and comigrated with mature IFN-alpha mRNA from virus-induced human peripheral blood leukocytes. No IFN-beta RNA transcripts were detected in any of the tissues tested. IFN-gamma mRNA was detected in only one sample of normal human spleen, which also contained an unusually high level of IFN-alpha mRNA. The use of a modified S1 mapping technique revealed the presence of IFN-alpha 1 and -alpha 2 transcripts only. No IFN-alpha 4, -alpha 5, -alpha 6, -alpha 7, -alpha 8, or -alpha 14 transcripts were detected in the same sample. The detection, in all the samples tested, of a characteristic pattern of expression of IFN genes, different from that obtained following induction, together with the low number of transcripts present (less than or equal to 0.03 copy per cell) suggest that specific IFN genes are transcribed constitutively in vivo.

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Selected References

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

  1. Aguet M., Blanchard B. High affinity binding of 125I-Labeled mouse interferon to a specific cell surface receptor. II. Analysis of binding properties. Virology. 1981 Dec;115(2):249–261. doi: 10.1016/0042-6822(81)90108-2. [DOI] [PubMed] [Google Scholar]
  2. Belardelli F., Vignaux F., Proietti E., Gresser I. Injection of mice with antibody to interferon renders peritoneal macrophages permissive for vesicular stomatitis virus and encephalomyocarditis virus. Proc Natl Acad Sci U S A. 1984 Jan;81(2):602–606. doi: 10.1073/pnas.81.2.602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Content J., De Wit L., Poupart P., Opdenakker G., Van Damme J., Billiau A. Induction of a 26-kDa-protein mRNA in human cells treated with an interleukin-1-related, leukocyte-derived factor. Eur J Biochem. 1985 Oct 15;152(2):253–257. doi: 10.1111/j.1432-1033.1985.tb09191.x. [DOI] [PubMed] [Google Scholar]
  5. DeStefano E., Friedman R. M., Friedman-Kien A. E., Goedert J. J., Henriksen D., Preble O. T., Sonnabend J. A., Vilcek J. Acid-labile human leukocyte interferon in homosexual men with Kaposi's sarcoma and lymphadenopathy. J Infect Dis. 1982 Oct;146(4):451–459. doi: 10.1093/infdis/146.4.451. [DOI] [PubMed] [Google Scholar]
  6. Dreiding P., Staeheli P., Haller O. Interferon-induced protein Mx accumulates in nuclei of mouse cells expressing resistance to influenza viruses. Virology. 1985 Jan 15;140(1):192–196. doi: 10.1016/0042-6822(85)90460-x. [DOI] [PubMed] [Google Scholar]
  7. Friedman R. L., Manly S. P., McMahon M., Kerr I. M., Stark G. R. Transcriptional and posttranscriptional regulation of interferon-induced gene expression in human cells. Cell. 1984 Oct;38(3):745–755. doi: 10.1016/0092-8674(84)90270-8. [DOI] [PubMed] [Google Scholar]
  8. GRESSER I., CHANY C. MULTIPLICATION OF POLIOVIRUS TYPE I IN PREPARATIONS OF HUMAN LEUKOCYTES AND ITS INHIBITION BY INTERFERON. J Immunol. 1964 Jun;92:889–895. [PubMed] [Google Scholar]
  9. Galabru J., Robert N., Buffet-Janvresse C., Rivière Y., Hovanessian A. G. Continuous production of interferon in normal mice: effect of anti-interferon globulin, sex, age, strain and environment on the levels of 2-5A synthetase and p67K kinase. J Gen Virol. 1985 Apr;66(Pt 4):711–718. doi: 10.1099/0022-1317-66-4-711. [DOI] [PubMed] [Google Scholar]
  10. Gray P. W., Goeddel D. V. Structure of the human immune interferon gene. Nature. 1982 Aug 26;298(5877):859–863. doi: 10.1038/298859a0. [DOI] [PubMed] [Google Scholar]
  11. Gresser I., Belardelli F., Maury C., Maunoury M. T., Tovey M. G. Injection of mice with antibody to interferon enhances the growth of transplantable murine tumors. J Exp Med. 1983 Dec 1;158(6):2095–2107. doi: 10.1084/jem.158.6.2095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gresser I., Tovey M. G. Antitumor effects of interferon. Biochim Biophys Acta. 1978 Oct 27;516(2):231–247. doi: 10.1016/0304-419x(78)90009-4. [DOI] [PubMed] [Google Scholar]
  13. Gresser I., Vignaux F., Belardelli F., Tovey M. G., Maunoury M. T. Injection of mice with antibody to mouse interferon alpha/beta decreases the level of 2'-5' oligoadenylate synthetase in peritoneal macrophages. J Virol. 1985 Jan;53(1):221–227. doi: 10.1128/jvi.53.1.221-227.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hager L. J., Palmiter R. D. Transcriptional regulation of mouse liver metallothionein-I gene by glucocorticoids. Nature. 1981 May 28;291(5813):340–342. doi: 10.1038/291340a0. [DOI] [PubMed] [Google Scholar]
  15. Heintz N., Sive H. L., Roeder R. G. Regulation of human histone gene expression: kinetics of accumulation and changes in the rate of synthesis and in the half-lives of individual histone mRNAs during the HeLa cell cycle. Mol Cell Biol. 1983 Apr;3(4):539–550. doi: 10.1128/mcb.3.4.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Henco K., Brosius J., Fujisawa A., Fujisawa J. I., Haynes J. R., Hochstadt J., Kovacic T., Pasek M., Schamböck A., Schmid J. Structural relationship of human interferon alpha genes and pseudogenes. J Mol Biol. 1985 Sep 20;185(2):227–260. doi: 10.1016/0022-2836(85)90401-2. [DOI] [PubMed] [Google Scholar]
  17. Hirano T., Yasukawa K., Harada H., Taga T., Watanabe Y., Matsuda T., Kashiwamura S., Nakajima K., Koyama K., Iwamatsu A. Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature. 1986 Nov 6;324(6092):73–76. doi: 10.1038/324073a0. [DOI] [PubMed] [Google Scholar]
  18. Hiscott J., Cantell K., Weissmann C. Differential expression of human interferon genes. Nucleic Acids Res. 1984 May 11;12(9):3727–3746. doi: 10.1093/nar/12.9.3727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hofer E., Hofer-Warbinek R., Darnell J. E., Jr Globin RNA transcription: a possible termination site and demonstration of transcriptional control correlated with altered chromatin structure. Cell. 1982 Jul;29(3):887–893. doi: 10.1016/0092-8674(82)90450-0. [DOI] [PubMed] [Google Scholar]
  20. Hooks J. J., Moutsopoulos H. M., Geis S. A., Stahl N. I., Decker J. L., Notkins A. L. Immune interferon in the circulation of patients with autoimmune disease. N Engl J Med. 1979 Jul 5;301(1):5–8. doi: 10.1056/NEJM197907053010102. [DOI] [PubMed] [Google Scholar]
  21. Horn Y., Zeidman J. L., Heller A., Hacohen D., Salzberg S. Serum interferon as a biological marker in malignant tumors. Oncology. 1985;42(3):164–168. doi: 10.1159/000226024. [DOI] [PubMed] [Google Scholar]
  22. Lebon P., Girard S., Thépot F., Chany C. The presence of alpha-interferon in human amniotic fluid. J Gen Virol. 1982 Apr;59(Pt 2):393–396. doi: 10.1099/0022-1317-59-2-393. [DOI] [PubMed] [Google Scholar]
  23. Lehrach H., Diamond D., Wozney J. M., Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. doi: 10.1021/bi00640a033. [DOI] [PubMed] [Google Scholar]
  24. Mantei N., Weissmann C. Controlled transcription of a human alpha-interferon gene introduced into mouse L cells. Nature. 1982 May 13;297(5862):128–132. doi: 10.1038/297128a0. [DOI] [PubMed] [Google Scholar]
  25. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mory Y., Chernajovsky Y., Feinstein S. I., Chen L., Nir U., Weissenbach J., Malpiece Y., Tiollais P., Marks D., Ladner M. Synthesis of human interferon beta 1 in Escherichia coli infected by a lambda phage recombinant containing a human genomic fragment. Eur J Biochem. 1981 Nov;120(1):197–202. doi: 10.1111/j.1432-1033.1981.tb05689.x. [DOI] [PubMed] [Google Scholar]
  27. Nagata S., Mantei N., Weissmann C. The structure of one of the eight or more distinct chromosomal genes for human interferon-alpha. Nature. 1980 Oct 2;287(5781):401–408. doi: 10.1038/287401a0. [DOI] [PubMed] [Google Scholar]
  28. Preble O. T., Black R. J., Friedman R. M., Klippel J. H., Vilcek J. Systemic lupus erythematosus: presence in human serum of an unusual acid-labile leukocyte interferon. Science. 1982 Apr 23;216(4544):429–431. doi: 10.1126/science.6176024. [DOI] [PubMed] [Google Scholar]
  29. Ragg H., Weissmann C. Not more than 117 base pairs of 5'-flanking sequence are required for inducible expression of a human IFN-alpha gene. Nature. 1983 Jun 2;303(5916):439–442. doi: 10.1038/303439a0. [DOI] [PubMed] [Google Scholar]
  30. Reid L. M., Minato N., Gresser I., Holland J., Kadish A., Bloom B. R. Influence of anti-mouse interferon serum on the growth and metastasis of tumor cells persistently infected with virus and of human prostatic tumors in athymic nude mice. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1171–1175. doi: 10.1073/pnas.78.2.1171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Resnitzky D., Yarden A., Zipori D., Kimchi A. Autocrine beta-related interferon controls c-myc suppression and growth arrest during hematopoietic cell differentiation. Cell. 1986 Jul 4;46(1):31–40. doi: 10.1016/0092-8674(86)90857-3. [DOI] [PubMed] [Google Scholar]
  32. Sen G. C. Mechanism of interferon action: progress toward its understanding. Prog Nucleic Acid Res Mol Biol. 1982;27:105–156. doi: 10.1016/s0079-6603(08)60599-1. [DOI] [PubMed] [Google Scholar]
  33. Sood A. K., Pereira D., Weissman S. M. Isolation and partial nucleotide sequence of a cDNA clone for human histocompatibility antigen HLA-B by use of an oligodeoxynucleotide primer. Proc Natl Acad Sci U S A. 1981 Jan;78(1):616–620. doi: 10.1073/pnas.78.1.616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Streuli M., Nagata S., Weissmann C. At least three human type alpha interferons: structure of alpha 2. Science. 1980 Sep 19;209(4463):1343–1347. doi: 10.1126/science.6158094. [DOI] [PubMed] [Google Scholar]
  35. Tsai S. Y., Tsai M. J., Lin C. T., O'Malley B. W. Effect of estrogen on ovalbumin gene expression in differentiated nontarget tissues. Biochemistry. 1979 Dec 11;18(25):5726–5731. doi: 10.1021/bi00592a032. [DOI] [PubMed] [Google Scholar]
  36. Weaver R. F., Weissmann C. Mapping of RNA by a modification of the Berk-Sharp procedure: the 5' termini of 15 S beta-globin mRNA precursor and mature 10 s beta-globin mRNA have identical map coordinates. Nucleic Acids Res. 1979 Nov 10;7(5):1175–1193. doi: 10.1093/nar/7.5.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Weidle U., Weissmann C. The 5'-flanking region of a human IFN-alpha gene mediates viral induction of transcription. Nature. 1983 Jun 2;303(5916):442–446. doi: 10.1038/303442a0. [DOI] [PubMed] [Google Scholar]
  38. Zilberstein A., Ruggieri R., Korn J. H., Revel M. Structure and expression of cDNA and genes for human interferon-beta-2, a distinct species inducible by growth-stimulatory cytokines. EMBO J. 1986 Oct;5(10):2529–2537. doi: 10.1002/j.1460-2075.1986.tb04531.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Zinn K., Maniatis T. Detection of factors that interact with the human beta-interferon regulatory region in vivo by DNAase I footprinting. Cell. 1986 May 23;45(4):611–618. doi: 10.1016/0092-8674(86)90293-x. [DOI] [PubMed] [Google Scholar]
  40. Zoumbos N. C., Gascon P., Djeu J. Y., Young N. S. Interferon is a mediator of hematopoietic suppression in aplastic anemia in vitro and possibly in vivo. Proc Natl Acad Sci U S A. 1985 Jan;82(1):188–192. doi: 10.1073/pnas.82.1.188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Zullo J. N., Cochran B. H., Huang A. S., Stiles C. D. Platelet-derived growth factor and double-stranded ribonucleic acids stimulate expression of the same genes in 3T3 cells. Cell. 1985 Dec;43(3 Pt 2):793–800. doi: 10.1016/0092-8674(85)90252-1. [DOI] [PubMed] [Google Scholar]

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