Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1986 Mar;83(6):1670–1674. doi: 10.1073/pnas.83.6.1670

Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators.

D Caput, B Beutler, K Hartog, R Thayer, S Brown-Shimer, A Cerami
PMCID: PMC323145  PMID: 2419912

Abstract

Recently, cDNA sequences have been reported for both human and murine tumor necrosis factor (TNF; cachectin). The coding region of the TNF genes is highly conserved between man and mouse; 80% homology is apparent at the amino acid level. We now observe that a 33-nucleotide sequence, comprised entirely of A and T residues and located in the 3'-untranslated region, is conserved in toto in the murine and human TNF mRNAs. Since the 3'-untranslated region is normally not conserved, we reasoned that this sequence might play a regulatory role. We identified a consensus sequence (TTATTTAT) present in the 3'-untranslated region of both human and mouse TNF mRNAs, as well as the mRNAs encoding human lymphotoxin, human colony stimulating factor, human and mouse interleukin 1, human and rat fibronectin, and most of the sequenced human and mouse interferons. All of these mRNAs, except the lymphotoxin mRNA, lack homology to the TNF mRNAs in the coding region. The consensus sequence is uncommon among mammalian mRNAs in general, but it appears with a frequency greater than chance alone would dictate, suggesting that it may serve a specific regulatory function among the mRNAs in which it is found. It is particularly prevalent among mRNAs encoding proteins related to the inflammatory response.

Full text

PDF
1670

Selected References

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

  1. Auron P. E., Webb A. C., Rosenwasser L. J., Mucci S. F., Rich A., Wolff S. M., Dinarello C. A. Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7907–7911. doi: 10.1073/pnas.81.24.7907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beisel W. R. Metabolic response to infection. Annu Rev Med. 1975;26:9–20. doi: 10.1146/annurev.me.26.020175.000301. [DOI] [PubMed] [Google Scholar]
  3. Beutler B. A., Milsark I. W., Cerami A. Cachectin/tumor necrosis factor: production, distribution, and metabolic fate in vivo. J Immunol. 1985 Dec;135(6):3972–3977. [PubMed] [Google Scholar]
  4. Beutler B., Greenwald D., Hulmes J. D., Chang M., Pan Y. C., Mathison J., Ulevitch R., Cerami A. Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. Nature. 1985 Aug 8;316(6028):552–554. doi: 10.1038/316552a0. [DOI] [PubMed] [Google Scholar]
  5. Beutler B., Mahoney J., Le Trang N., Pekala P., Cerami A. Purification of cachectin, a lipoprotein lipase-suppressing hormone secreted by endotoxin-induced RAW 264.7 cells. J Exp Med. 1985 May 1;161(5):984–995. doi: 10.1084/jem.161.5.984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Beutler B., Milsark I. W., Cerami A. C. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science. 1985 Aug 30;229(4716):869–871. doi: 10.1126/science.3895437. [DOI] [PubMed] [Google Scholar]
  7. Cerami A., Ikeda Y., Le Trang N., Hotez P. J., Beutler B. Weight loss associated with an endotoxin-induced mediator from peritoneal macrophages: the role of cachectin (tumor necrosis factor). Immunol Lett. 1985;11(3-4):173–177. doi: 10.1016/0165-2478(85)90165-8. [DOI] [PubMed] [Google Scholar]
  8. Dayer J. M., Beutler B., Cerami A. Cachectin/tumor necrosis factor stimulates collagenase and prostaglandin E2 production by human synovial cells and dermal fibroblasts. J Exp Med. 1985 Dec 1;162(6):2163–2168. doi: 10.1084/jem.162.6.2163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dente L., Ciliberto G., Cortese R. Structure of the human alpha 1-acid glycoprotein gene: sequence homology with other human acute phase protein genes. Nucleic Acids Res. 1985 Jun 11;13(11):3941–3952. doi: 10.1093/nar/13.11.3941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Favaloro J., Treisman R., Kamen R. Transcription maps of polyoma virus-specific RNA: analysis by two-dimensional nuclease S1 gel mapping. Methods Enzymol. 1980;65(1):718–749. doi: 10.1016/s0076-6879(80)65070-8. [DOI] [PubMed] [Google Scholar]
  11. Filkins J. P. Monokines and the metabolic pathophysiology of septic shock. Fed Proc. 1985 Feb;44(2):300–304. [PubMed] [Google Scholar]
  12. Fransen L., Müller R., Marmenout A., Tavernier J., Van der Heyden J., Kawashima E., Chollet A., Tizard R., Van Heuverswyn H., Van Vliet A. Molecular cloning of mouse tumour necrosis factor cDNA and its eukaryotic expression. Nucleic Acids Res. 1985 Jun 25;13(12):4417–4429. doi: 10.1093/nar/13.12.4417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gough N. M., Gough J., Metcalf D., Kelso A., Grail D., Nicola N. A., Burgess A. W., Dunn A. R. Molecular cloning of cDNA encoding a murine haematopoietic growth regulator, granulocyte-macrophage colony stimulating factor. 1984 Jun 28-Jul 4Nature. 309(5971):763–767. doi: 10.1038/309763a0. [DOI] [PubMed] [Google Scholar]
  14. Gray P. W., Aggarwal B. B., Benton C. V., Bringman T. S., Henzel W. J., Jarrett J. A., Leung D. W., Moffat B., Ng P., Svedersky L. P. Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumour necrosis activity. Nature. 1984 Dec 20;312(5996):721–724. doi: 10.1038/312721a0. [DOI] [PubMed] [Google Scholar]
  15. Hotez P. J., Le Trang N., Fairlamb A. H., Cerami A. Lipoprotein lipase suppression in 3T3-L1 cells by a haematoprotozoan-induced mediator from peritoneal exudate cells. Parasite Immunol. 1984 May;6(3):203–209. doi: 10.1111/j.1365-3024.1984.tb00793.x. [DOI] [PubMed] [Google Scholar]
  16. Kawakami M., Cerami A. Studies of endotoxin-induced decrease in lipoprotein lipase activity. J Exp Med. 1981 Sep 1;154(3):631–639. doi: 10.1084/jem.154.3.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lomedico P. T., Gubler U., Hellmann C. P., Dukovich M., Giri J. G., Pan Y. C., Collier K., Semionow R., Chua A. O., Mizel S. B. Cloning and expression of murine interleukin-1 cDNA in Escherichia coli. 1984 Nov 29-Dec 5Nature. 312(5993):458–462. doi: 10.1038/312458a0. [DOI] [PubMed] [Google Scholar]
  18. Mahoney J. R., Jr, Beutler B. A., Le Trang N., Vine W., Ikeda Y., Kawakami M., Cerami A. Lipopolysaccharide-treated RAW 264.7 cells produce a mediator that inhibits lipoprotein lipase in 3T3-L1 cells. J Immunol. 1985 Mar;134(3):1673–1675. [PubMed] [Google Scholar]
  19. March C. J., Mosley B., Larsen A., Cerretti D. P., Braedt G., Price V., Gillis S., Henney C. S., Kronheim S. R., Grabstein K. Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature. 1985 Jun 20;315(6021):641–647. doi: 10.1038/315641a0. [DOI] [PubMed] [Google Scholar]
  20. Nei M., Li W. H. Mathematical model for studying genetic variation in terms of restriction endonucleases. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5269–5273. doi: 10.1073/pnas.76.10.5269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pennica D., Nedwin G. E., Hayflick J. S., Seeburg P. H., Derynck R., Palladino M. A., Kohr W. J., Aggarwal B. B., Goeddel D. V. Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature. 1984 Dec 20;312(5996):724–729. doi: 10.1038/312724a0. [DOI] [PubMed] [Google Scholar]
  22. Rouzer C. A., Cerami A. Hypertriglyceridemia associated with Trypanosoma brucei brucei infection in rabbits: role of defective triglyceride removal. Mol Biochem Parasitol. 1980 Oct;2(1):31–38. doi: 10.1016/0166-6851(80)90046-8. [DOI] [PubMed] [Google Scholar]
  23. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Torti F. M., Dieckmann B., Beutler B., Cerami A., Ringold G. M. A macrophage factor inhibits adipocyte gene expression: an in vitro model of cachexia. Science. 1985 Aug 30;229(4716):867–869. doi: 10.1126/science.3839597. [DOI] [PubMed] [Google Scholar]
  25. Wong G. G., Witek J. S., Temple P. A., Wilkens K. M., Leary A. C., Luxenberg D. P., Jones S. S., Brown E. L., Kay R. M., Orr E. C. Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins. Science. 1985 May 17;228(4701):810–815. doi: 10.1126/science.3923623. [DOI] [PubMed] [Google Scholar]
  26. Yaffe D., Nudel U., Mayer Y., Neuman S. Highly conserved sequences in the 3' untranslated region of mRNAs coding for homologous proteins in distantly related species. Nucleic Acids Res. 1985 May 24;13(10):3723–3737. doi: 10.1093/nar/13.10.3723. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES