Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Dec;86(6):2154–2160. doi: 10.1172/JCI114954

Anti-(U1) small nuclear RNA antibodies in anti-small nuclear ribonucleoprotein sera from patients with connective tissue diseases.

W J van Venrooij 1, R Hoet 1, J Castrop 1, B Hageman 1, I W Mattaj 1, L B van de Putte 1
PMCID: PMC329856  PMID: 1701452

Abstract

Small nuclear ribonucleoprotein (snRNP) particles are a class of RNA-containing particles in the nucleus of eukaryotic cells. Sera from patients with connective tissue diseases often contain antibodies against the proteins present in these snRNPs. Antibodies against the RNA components of snRNPs, the U snRNAs, are thought to be rare. We tested 118 anti-snRNP sera for the presence of anti-snRNA antibodies and found them in 45 sera (38%). In all sera the antibodies (IgG and F(ab)2 fragments thereof) were exclusively directed against U1 snRNA. The anti-(U1) RNA antibodies were always accompanied by anti-(U1)RNP antibodies but were not found in sera which contain antibodies of the Sm serotype directed against all nucleoplasmic U snRNP particles. Like anti-RNP antibodies, anti-U1 RNA activity is confined to sera from patients with SLE or SLE overlap syndromes and is rarely found in patients with other connective tissue diseases. By analyzing binding to subfragments of U1 snRNA made in vitro, it was demonstrated that anti-(U1)RNA antibodies recognize epitopes distributed throughout the U1 RNA molecule. In most sera, however, either the second or the fourth hairpin loop is the main target of the antibody. The possible mechanisms that could lead to the production of this new type of autoantibody are discussed.

Full text

PDF
2160

Images in this article

Selected References

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

  1. Branlant C., Krol A., Ebel J. P., Lazar E., Haendler B., Jacob M. U2 RNA shares a structural domain with U1, U4, and U5 RNAs. EMBO J. 1982;1(10):1259–1265. doi: 10.1002/j.1460-2075.1982.tb00022.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chan E. K., Tan E. M. Epitopic targets for autoantibodies in systemic lupus erythematosus and Sjögren's syndrome. Curr Opin Rheumatol. 1989 Oct;1(3):376–381. doi: 10.1097/00002281-198901030-00022. [DOI] [PubMed] [Google Scholar]
  3. Dandekar T., Tollervey D. Cloning of Schizosaccharomyces pombe genes encoding the U1, U2, U3 and U4 snRNAs. Gene. 1989 Sep 30;81(2):227–235. doi: 10.1016/0378-1119(89)90183-2. [DOI] [PubMed] [Google Scholar]
  4. Deutscher S. L., Keene J. D. A sequence-specific conformational epitope on U1 RNA is recognized by a unique autoantibody. Proc Natl Acad Sci U S A. 1988 May;85(10):3299–3303. doi: 10.1073/pnas.85.10.3299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Eilat D., Hochberg M., Fischel R., Laskov R. Antibodies to RNA from autoimmune NZB/NZW mice recognize a similar antigenic determinant and show a large idiotypic diversity. Proc Natl Acad Sci U S A. 1982 Jun;79(12):3818–3822. doi: 10.1073/pnas.79.12.3818. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Eilat D., Steinberg A. D., Schechter A. N. The reaction of SLE antibodies with native, single stranded RNA: radioassay and binding specificities. J Immunol. 1978 Feb;120(2):550–557. [PubMed] [Google Scholar]
  7. Habets W. J., de Rooij D. J., Hoet M. H., van de Putte L. B., van Venrooij W. J. Quantitation of anti-RNP and anti-Sm antibodies in MCTD and SLE patients by immunoblotting. Clin Exp Immunol. 1985 Feb;59(2):457–466. [PMC free article] [PubMed] [Google Scholar]
  8. Habets W., Hoet M., Bringmann P., Lührmann R., van Venrooij W. Autoantibodies to ribonucleoprotein particles containing U2 small nuclear RNA. EMBO J. 1985 Jun;4(6):1545–1550. doi: 10.1002/j.1460-2075.1985.tb03815.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hamm J., Dathan N. A., Scherly D., Mattaj I. W. Multiple domains of U1 snRNA, including U1 specific protein binding sites, are required for splicing. EMBO J. 1990 Apr;9(4):1237–1244. doi: 10.1002/j.1460-2075.1990.tb08231.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hamm J., Kazmaier M., Mattaj I. W. In vitro assembly of U1 snRNPs. EMBO J. 1987 Nov;6(11):3479–3485. doi: 10.1002/j.1460-2075.1987.tb02672.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kastner B., Bach M., Lührmann R. Electron microscopy of small nuclear ribonucleoprotein (snRNP) particles U2 and U5: evidence for a common structure-determining principle in the major U snRNP family. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1710–1714. doi: 10.1073/pnas.87.5.1710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kurata N., Tan E. M. Identification of antibodies to nuclear acidic antigens by counterimmunoelectrophoresis. Arthritis Rheum. 1976 May-Jun;19(3):574–580. doi: 10.1002/art.1780190309. [DOI] [PubMed] [Google Scholar]
  13. Lutz-Freyermuth C., Keene J. D., Lutz-Reyermuth C. The U1 RNA-binding site of the U1 small nuclear ribonucleoprotein (snRNP)-associated A protein suggests a similarity with U2 snRNPs. Mol Cell Biol. 1989 Jul;9(7):2975–2982. doi: 10.1128/mcb.9.7.2975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Patton J. R., Habets W., van Venrooij W. J., Pederson T. U1 small nuclear ribonucleoprotein particle-specific proteins interact with the first and second stem-loops of U1 RNA, with the A protein binding directly to the RNA independently of the 70K and Sm proteins. Mol Cell Biol. 1989 Aug;9(8):3360–3368. doi: 10.1128/mcb.9.8.3360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Porter G., Brennwald P., Wise J. A. U1 small nuclear RNA from Schizosaccharomyces pombe has unique and conserved features and is encoded by an essential single-copy gene. Mol Cell Biol. 1990 Jun;10(6):2874–2881. doi: 10.1128/mcb.10.6.2874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pruijn G. J., Slobbe R. L., Van Venrooij W. J. Structure and function of La and Ro RNPs. Mol Biol Rep. 1990;14(2-3):43–48. doi: 10.1007/BF00360410. [DOI] [PubMed] [Google Scholar]
  17. Query C. C., Bentley R. C., Keene J. D. A specific 31-nucleotide domain of U1 RNA directly interacts with the 70K small nuclear ribonucleoprotein component. Mol Cell Biol. 1989 Nov;9(11):4872–4881. doi: 10.1128/mcb.9.11.4872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Scherly D., Boelens W., Dathan N. A., van Venrooij W. J., Mattaj I. W. Major determinants of the specificity of interaction between small nuclear ribonucleoproteins U1A and U2B'' and their cognate RNAs. Nature. 1990 Jun 7;345(6275):502–506. doi: 10.1038/345502a0. [DOI] [PubMed] [Google Scholar]
  19. Scherly D., Boelens W., van Venrooij W. J., Dathan N. A., Hamm J., Mattaj I. W. Identification of the RNA binding segment of human U1 A protein and definition of its binding site on U1 snRNA. EMBO J. 1989 Dec 20;8(13):4163–4170. doi: 10.1002/j.1460-2075.1989.tb08601.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Spencer-Green G., Kelley L., Adams L. E., Donovan-Brand R., Hess E. V. Polynucleotide antibodies in connective tissue disease: viral markers or disease mediators? J Lab Clin Med. 1986 Feb;107(2):159–165. [PubMed] [Google Scholar]
  21. Surowy C. S., van Santen V. L., Scheib-Wixted S. M., Spritz R. A. Direct, sequence-specific binding of the human U1-70K ribonucleoprotein antigen protein to loop I of U1 small nuclear RNA. Mol Cell Biol. 1989 Oct;9(10):4179–4186. doi: 10.1128/mcb.9.10.4179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Van Venrooij W. J., Sillekens P. T. Small nuclear RNA associated proteins: autoantigens in connective tissue diseases. Clin Exp Rheumatol. 1989 Nov-Dec;7(6):635–645. [PubMed] [Google Scholar]
  24. Wilusz J., Keene J. D. Autoantibodies specific for U1 RNA and initiator methionine tRNA. J Biol Chem. 1986 Apr 25;261(12):5467–5472. [PubMed] [Google Scholar]
  25. de Rooij D. J., van de Putte L. B., Habets W. J., Verbeek A. L., van Venrooij W. J. The use of immunoblotting to detect antibodies to nuclear and cytoplasmic antigens. Clinical and serological associations in rheumatic diseases. Scand J Rheumatol. 1988;17(5):353–364. doi: 10.3109/03009748809105271. [DOI] [PubMed] [Google Scholar]
  26. van Eekelen C. A., van Venrooij W. J. hnRNA and its attachment to a nuclear protein matrix. J Cell Biol. 1981 Mar;88(3):554–563. doi: 10.1083/jcb.88.3.554. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES