Skip to main content
NCBI home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1995 Jul 25;23(14):2770–2774. doi: 10.1093/nar/23.14.2770

Identification of human autoantibodies to transcription factor IIB.

F D Abendroth 1, S R Peterson 1, M Galman 1, A Suwa 1, J A Hardin 1, W S Dynan 1
PMCID: PMC307103  PMID: 7651839

Abstract

We have characterized the ability of various human autoimmune sera to react with RNA polymerase II transcription factors. One serum, which strongly inhibited transcription in a cell-free system, was shown to contain antibodies directed against human TFIIB. The serum did not show reactivity against the other general transcription factors, including human TBP, TFIIE and TFIIF. The inhibition of transcription was directly attributable to depletion of TFIIB activity, as demonstrated by reconstitution of activity with recombinant TFIIB. It has long been recognized that components of the RNA processing machinery are major human autoantigens. The present results show that at least one general transcription factor required for messenger RNA synthesis is an autoantigen as well.

Full text

PDF
2770

Images in this article

2771Image
on p.2771
2772Image
on p.2772
2772Image
on p.2772
2773Image
on p.2773

Selected References

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

  1. Arias J. A., Dynan W. S. Promoter-dependent transcription by RNA polymerase II using immobilized enzyme complexes. J Biol Chem. 1989 Feb 25;264(6):3223–3229. [PubMed] [Google Scholar]
  2. Arias J. A., Peterson S. R., Dynan W. S. Promoter-dependent phosphorylation of RNA polymerase II by a template-bound kinase. Association with transcriptional initiation. J Biol Chem. 1991 May 5;266(13):8055–8061. [PubMed] [Google Scholar]
  3. Carey M., Leatherwood J., Ptashne M. A potent GAL4 derivative activates transcription at a distance in vitro. Science. 1990 Feb 9;247(4943):710–712. doi: 10.1126/science.2405489. [DOI] [PubMed] [Google Scholar]
  4. Carey M., Lin Y. S., Green M. R., Ptashne M. A mechanism for synergistic activation of a mammalian gene by GAL4 derivatives. Nature. 1990 May 24;345(6273):361–364. doi: 10.1038/345361a0. [DOI] [PubMed] [Google Scholar]
  5. Chan E. K., Imai H., Hamel J. C., Tan E. M. Human autoantibody to RNA polymerase I transcription factor hUBF. Molecular identity of nucleolus organizer region autoantigen NOR-90 and ribosomal RNA transcription upstream binding factor. J Exp Med. 1991 Nov 1;174(5):1239–1244. doi: 10.1084/jem.174.5.1239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Finkelstein A., Kostrub C. F., Li J., Chavez D. P., Wang B. Q., Fang S. M., Greenblatt J., Burton Z. F. A cDNA encoding RAP74, a general initiation factor for transcription by RNA polymerase II. Nature. 1992 Jan 30;355(6359):464–467. doi: 10.1038/355464a0. [DOI] [PubMed] [Google Scholar]
  7. Gottlieb E., Steitz J. A. Function of the mammalian La protein: evidence for its action in transcription termination by RNA polymerase III. EMBO J. 1989 Mar;8(3):851–861. doi: 10.1002/j.1460-2075.1989.tb03446.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gottlieb E., Steitz J. A. The RNA binding protein La influences both the accuracy and the efficiency of RNA polymerase III transcription in vitro. EMBO J. 1989 Mar;8(3):841–850. doi: 10.1002/j.1460-2075.1989.tb03445.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ha I., Lane W. S., Reinberg D. Cloning of a human gene encoding the general transcription initiation factor IIB. Nature. 1991 Aug 22;352(6337):689–695. doi: 10.1038/352689a0. [DOI] [PubMed] [Google Scholar]
  10. Hirakata M., Okano Y., Pati U., Suwa A., Medsger T. A., Jr, Hardin J. A., Craft J. Identification of autoantibodies to RNA polymerase II. Occurrence in systemic sclerosis and association with autoantibodies to RNA polymerases I and III. J Clin Invest. 1993 Jun;91(6):2665–2672. doi: 10.1172/JCI116505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Imai H., Fritzler M. J., Neri R., Bombardieri S., Tan E. M., Chan E. K. Immunocytochemical characterization of human NOR-90 (upstream binding factor) and associated antigens reactive with autoimmune sera. Two MR forms of NOR-90/hUBF autoantigens. Mol Biol Rep. 1994 Mar;19(2):115–124. doi: 10.1007/BF00997157. [DOI] [PubMed] [Google Scholar]
  12. Kuwana M., Kaburaki J., Mimori T., Tojo T., Homma M. Autoantibody reactive with three classes of RNA polymerases in sera from patients with systemic sclerosis. J Clin Invest. 1993 Apr;91(4):1399–1404. doi: 10.1172/JCI116343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lagaye S., Barque J. P., le Maire M., Denis H., Larsen C. J. Characterization by human antibodies of two HeLa cell proteins which are related to Xenopus laevis transcription factor TFIIIA. Nucleic Acids Res. 1988 Mar 25;16(6):2473–2487. doi: 10.1093/nar/16.6.2473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lin Y. S., Carey M. F., Ptashne M., Green M. R. GAL4 derivatives function alone and synergistically with mammalian activators in vitro. Cell. 1988 Aug 26;54(5):659–664. doi: 10.1016/s0092-8674(88)80010-2. [DOI] [PubMed] [Google Scholar]
  15. Mimori T., Ohosone Y., Hama N., Suwa A., Akizuki M., Homma M., Griffith A. J., Hardin J. A. Isolation and characterization of cDNA encoding the 80-kDa subunit protein of the human autoantigen Ku (p70/p80) recognized by autoantibodies from patients with scleroderma-polymyositis overlap syndrome. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1777–1781. doi: 10.1073/pnas.87.5.1777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Okano Y., Steen V. D., Medsger T. A., Jr Autoantibody reactive with RNA polymerase III in systemic sclerosis. Ann Intern Med. 1993 Nov 15;119(10):1005–1013. doi: 10.7326/0003-4819-119-10-199311150-00007. [DOI] [PubMed] [Google Scholar]
  17. Padgett R. A., Mount S. M., Steitz J. A., Sharp P. A. Splicing of messenger RNA precursors is inhibited by antisera to small nuclear ribonucleoprotein. Cell. 1983 Nov;35(1):101–107. doi: 10.1016/0092-8674(83)90212-x. [DOI] [PubMed] [Google Scholar]
  18. Peterson M. G., Inostroza J., Maxon M. E., Flores O., Admon A., Reinberg D., Tjian R. Structure and functional properties of human general transcription factor IIE. Nature. 1991 Dec 5;354(6352):369–373. doi: 10.1038/354369a0. [DOI] [PubMed] [Google Scholar]
  19. Peterson M. G., Tanese N., Pugh B. F., Tjian R. Functional domains and upstream activation properties of cloned human TATA binding protein. Science. 1990 Jun 29;248(4963):1625–1630. doi: 10.1126/science.2363050. [DOI] [PubMed] [Google Scholar]
  20. Peterson S. R., Jesch S. A., Chamberlin T. N., Dvir A., Rabindran S. K., Wu C., Dynan W. S. Stimulation of the DNA-dependent protein kinase by RNA polymerase II transcriptional activator proteins. J Biol Chem. 1995 Jan 20;270(3):1449–1454. doi: 10.1074/jbc.270.3.1449. [DOI] [PubMed] [Google Scholar]
  21. Reeves W. H., Sthoeger Z. M. Molecular cloning of cDNA encoding the p70 (Ku) lupus autoantigen. J Biol Chem. 1989 Mar 25;264(9):5047–5052. [PubMed] [Google Scholar]
  22. Reimer G., Rose K. M., Scheer U., Tan E. M. Autoantibody to RNA polymerase I in scleroderma sera. J Clin Invest. 1987 Jan;79(1):65–72. doi: 10.1172/JCI112809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Satoh M., Ajmani A. K., Ogasawara T., Langdon J. J., Hirakata M., Wang J., Reeves W. H. Autoantibodies to RNA polymerase II are common in systemic lupus erythematosus and overlap syndrome. Specific recognition of the phosphorylated (IIO) form by a subset of human sera. J Clin Invest. 1994 Nov;94(5):1981–1989. doi: 10.1172/JCI117550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Satoh M., Kuwana M., Ogasawara T., Ajmani A. K., Langdon J. J., Kimpel D., Wang J., Reeves W. H. Association of autoantibodies to topoisomerase I and the phosphorylated (IIO) form of RNA polymerase II in Japanese scleroderma patients. J Immunol. 1994 Dec 15;153(12):5838–5848. [PubMed] [Google Scholar]
  25. Sopta M., Burton Z. F., Greenblatt J. Structure and associated DNA-helicase activity of a general transcription initiation factor that binds to RNA polymerase II. Nature. 1989 Oct 5;341(6241):410–414. doi: 10.1038/341410a0. [DOI] [PubMed] [Google Scholar]
  26. Tan E. M. Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol. 1989;44:93–151. doi: 10.1016/s0065-2776(08)60641-0. [DOI] [PubMed] [Google Scholar]
  27. Yang V. W., Lerner M. R., Steitz J. A., Flint S. J. A small nuclear ribonucleoprotein is required for splicing of adenoviral early RNA sequences. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1371–1375. doi: 10.1073/pnas.78.3.1371. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES