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. 1993 Jul 15;90(14):6781–6785. doi: 10.1073/pnas.90.14.6781

Rare scleroderma autoantibodies to the U11 small nuclear ribonucleoprotein and to the trimethylguanosine cap of U small nuclear RNAs.

A C Gilliam 1, J A Steitz 1
PMCID: PMC47016  PMID: 8341699

Abstract

We have identified a scleroderma serum (Ru) with a previously undescribed specificity to protein components of the U11 small nuclear ribonucleoprotein particle (snRNP), a low-abundance member of the Sm class of U RNPs. The U11 RNP can be specifically immunoprecipitated from sonicated HeLa cells with Ru serum. In nuclear extracts, a fraction of the U11 particle is found complexed to the U12 RNP, an even lower abundance Sm snRNP. In glycerol gradient fractions, Ru serum identifies a 65-kDa protein that cosediments with the U11-U12 complex and is shifted upon targeted degradation of the U12 RNA. The 65-kDa protein therefore appears to be a component of the U11-U12 snRNP complex, whereas another Ru-reactive (140 kDa) protein may be associated with the free U11 RNP. The Ru serum also contains autoantibodies directed against the trimethylguanosine cap of U RNAs. This rare specificity has been described previously in only three other scleroderma patients.

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Selected References

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

  1. Behrens S. E., Lührmann R. Immunoaffinity purification of a [U4/U6.U5] tri-snRNP from human cells. Genes Dev. 1991 Aug;5(8):1439–1452. doi: 10.1101/gad.5.8.1439. [DOI] [PubMed] [Google Scholar]
  2. Bennett M., Michaud S., Kingston J., Reed R. Protein components specifically associated with prespliceosome and spliceosome complexes. Genes Dev. 1992 Oct;6(10):1986–2000. doi: 10.1101/gad.6.10.1986. [DOI] [PubMed] [Google Scholar]
  3. Black D. L., Chabot B., Steitz J. A. U2 as well as U1 small nuclear ribonucleoproteins are involved in premessenger RNA splicing. Cell. 1985 Oct;42(3):737–750. doi: 10.1016/0092-8674(85)90270-3. [DOI] [PubMed] [Google Scholar]
  4. Bochnig P., Reuter R., Bringmann P., Lührmann R. A monoclonal antibody against 2,2,7-trimethylguanosine that reacts with intact, class U, small nuclear ribonucleoproteins as well as with 7-methylguanosine-capped RNAs. Eur J Biochem. 1987 Oct 15;168(2):461–467. doi: 10.1111/j.1432-1033.1987.tb13439.x. [DOI] [PubMed] [Google Scholar]
  5. Bringmann P., Rinke J., Appel B., Reuter R., Lührmann R. Purification of snRNPs U1, U2, U4, U5 and U6 with 2,2,7-trimethylguanosine-specific antibody and definition of their constituent proteins reacting with anti-Sm and anti-(U1)RNP antisera. EMBO J. 1983;2(7):1129–1135. doi: 10.1002/j.1460-2075.1983.tb01557.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Christofori G., Keller W. 3' cleavage and polyadenylation of mRNA precursors in vitro requires a poly(A) polymerase, a cleavage factor, and a snRNP. Cell. 1988 Sep 9;54(6):875–889. doi: 10.1016/s0092-8674(88)91263-9. [DOI] [PubMed] [Google Scholar]
  7. Craft J., Mimori T., Olsen T. L., Hardin J. A. The U2 small nuclear ribonucleoprotein particle as an autoantigen. Analysis with sera from patients with overlap syndromes. J Clin Invest. 1988 Jun;81(6):1716–1724. doi: 10.1172/JCI113511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Donis-Keller H., Maxam A. M., Gilbert W. Mapping adenines, guanines, and pyrimidines in RNA. Nucleic Acids Res. 1977 Aug;4(8):2527–2538. doi: 10.1093/nar/4.8.2527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Donis-Keller H. Phy M: an RNase activity specific for U and A residues useful in RNA sequence analysis. Nucleic Acids Res. 1980 Jul 25;8(14):3133–3142. doi: 10.1093/nar/8.14.3133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. England T. E., Bruce A. G., Uhlenbeck O. C. Specific labeling of 3' termini of RNA with T4 RNA ligase. Methods Enzymol. 1980;65(1):65–74. doi: 10.1016/s0076-6879(80)65011-3. [DOI] [PubMed] [Google Scholar]
  12. Fujii T., Mimori T., Hama N., Suwa A., Akizuki M., Tojo T., Homma M. Characterization of autoantibodies that recognize U4/U6 small ribonucleoprotein particles in serum from a patient with primary Sjögren's syndrome. J Biol Chem. 1992 Aug 15;267(23):16412–16416. [PubMed] [Google Scholar]
  13. Horsfall A. C. Molecular mimicry and autoantigens in connective tissue diseases. Mol Biol Rep. 1992 Jun;16(3):139–147. doi: 10.1007/BF00464701. [DOI] [PubMed] [Google Scholar]
  14. Izaurralde E., Mattaj I. W. Transport of RNA between nucleus and cytoplasm. Semin Cell Biol. 1992 Aug;3(4):279–288. doi: 10.1016/1043-4682(92)90029-u. [DOI] [PubMed] [Google Scholar]
  15. Krainer A. R. Pre-mRNA splicing by complementation with purified human U1, U2, U4/U6 and U5 snRNPs. Nucleic Acids Res. 1988 Oct 25;16(20):9415–9429. doi: 10.1093/nar/16.20.9415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lehmeier T., Foulaki K., Lührmann R. Evidence for three distinct D proteins, which react differentially with anti-Sm autoantibodies, in the cores of the major snRNPs U1, U2, U4/U6 and U5. Nucleic Acids Res. 1990 Nov 25;18(22):6475–6484. doi: 10.1093/nar/18.22.6475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lerner E. A., Lerner M. R., Janeway C. A., Jr, Steitz J. A. Monoclonal antibodies to nucleic acid-containing cellular constituents: probes for molecular biology and autoimmune disease. Proc Natl Acad Sci U S A. 1981 May;78(5):2737–2741. doi: 10.1073/pnas.78.5.2737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lerner M. R., Boyle J. A., Hardin J. A., Steitz J. A. Two novel classes of small ribonucleoproteins detected by antibodies associated with lupus erythematosus. Science. 1981 Jan 23;211(4480):400–402. doi: 10.1126/science.6164096. [DOI] [PubMed] [Google Scholar]
  19. Lerner M. R., Steitz J. A. Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5495–5499. doi: 10.1073/pnas.76.11.5495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Luhrmann R., Appel B., Bringmann P., Rinke J., Reuter R., Rothe S., Bald R. Isolation and characterization of rabbit anti-m3 2,2,7G antibodies. Nucleic Acids Res. 1982 Nov 25;10(22):7103–7113. doi: 10.1093/nar/10.22.7103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mattaj I. W., Tollervey D., Séraphin B. Small nuclear RNAs in messenger RNA and ribosomal RNA processing. FASEB J. 1993 Jan;7(1):47–53. doi: 10.1096/fasebj.7.1.8422974. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Montzka K. A., Steitz J. A. Additional low-abundance human small nuclear ribonucleoproteins: U11, U12, etc. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8885–8889. doi: 10.1073/pnas.85.23.8885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Okano Y., Medsger T. A., Jr Newly identified U4/U6 snRNP-binding proteins by serum autoantibodies from a patient with systemic sclerosis. J Immunol. 1991 Jan 15;146(2):535–542. [PubMed] [Google Scholar]
  25. Okano Y., Medsger T. A., Jr Novel human autoantibodies reactive with 5'-terminal trimethylguanosine cap structures of U small nuclear RNA. J Immunol. 1992 Aug 1;149(3):1093–1098. [PubMed] [Google Scholar]
  26. Pettersson I., Hinterberger M., Mimori T., Gottlieb E., Steitz J. A. The structure of mammalian small nuclear ribonucleoproteins. Identification of multiple protein components reactive with anti-(U1)ribonucleoprotein and anti-Sm autoantibodies. J Biol Chem. 1984 May 10;259(9):5907–5914. [PubMed] [Google Scholar]
  27. Ryner L. C., Takagaki Y., Manley J. L. Sequences downstream of AAUAAA signals affect pre-mRNA cleavage and polyadenylation in vitro both directly and indirectly. Mol Cell Biol. 1989 Apr;9(4):1759–1771. doi: 10.1128/mcb.9.4.1759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schattner A., Rager-Zisman B. Virus-induced autoimmunity. Rev Infect Dis. 1990 Mar-Apr;12(2):204–222. doi: 10.1093/clinids/12.2.204. [DOI] [PubMed] [Google Scholar]
  29. Sharp G. C., Irvin W. S., LaRoque R. L., Velez C., Daly V., Kaiser A. D., Holman H. R. Association of autoantibodies to different nuclear antigens with clinical patterns of rheumatic disease and responsiveness to therapy. J Clin Invest. 1971 Feb;50(2):350–359. doi: 10.1172/JCI106502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Smith H. O., Tabiti K., Schaffner G., Soldati D., Albrecht U., Birnstiel M. L. Two-step affinity purification of U7 small nuclear ribonucleoprotein particles using complementary biotinylated 2'-O-methyl oligoribonucleotides. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9784–9788. doi: 10.1073/pnas.88.21.9784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sontheimer E. J., Steitz J. A. Three novel functional variants of human U5 small nuclear RNA. Mol Cell Biol. 1992 Feb;12(2):734–746. doi: 10.1128/mcb.12.2.734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Stollar B. D. Antibodies to DNA. CRC Crit Rev Biochem. 1986;20(1):1–36. doi: 10.3109/10409238609115899. [DOI] [PubMed] [Google Scholar]
  33. Suter-Crazzolara C., Keller W. Organization and transient expression of the gene for human U11 snRNA. Gene Expr. 1991 May;1(2):91–102. [PMC free article] [PubMed] [Google Scholar]
  34. 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]
  35. Wassarman K. M., Steitz J. A. The low-abundance U11 and U12 small nuclear ribonucleoproteins (snRNPs) interact to form a two-snRNP complex. Mol Cell Biol. 1992 Mar;12(3):1276–1285. doi: 10.1128/mcb.12.3.1276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Zieve G. W., Sauterer R. A. Cell biology of the snRNP particles. Crit Rev Biochem Mol Biol. 1990;25(1):1–46. doi: 10.3109/10409239009090604. [DOI] [PubMed] [Google Scholar]

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