Abstract
A cDNA library was prepared from peripheral blood lymphocytes of an autoimmune patient with primary Sjogrens' syndrome. The cDNA library was screened with the patients own autoimmune serum being monospecific for the nuclear autoantigen La/SS-B. Thereby an alternative type of La mRNA was identified that differed from the known La mRNA due to an exchange of the exon 1. Sequencing of the genomic region between the exons 1 and 2 showed that the alternative 5'-end is a part of the intron. In addition, the presence of an alternative promoter site, which exists within the intron downstream of the exon 1, became evident. In consequence, the alternative La mRNA is the result of a promoter switching combined with an alternative splicing mechanism. In the intron, further transcription factor binding sites, including a NF- kappa B element, were identified leading to the suggestion that the expression of the gene encoding for the nuclear autoantigen La/SS-B alters in dependence on disease conditions.
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- Chambers J. C., Keene J. D. Isolation and analysis of cDNA clones expressing human lupus La antigen. Proc Natl Acad Sci U S A. 1985 Apr;82(7):2115–2119. doi: 10.1073/pnas.82.7.2115. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chambers J. C., Kenan D., Martin B. J., Keene J. D. Genomic structure and amino acid sequence domains of the human La autoantigen. J Biol Chem. 1988 Dec 5;263(34):18043–18051. [PubMed] [Google Scholar]
- Chan E. K., Sullivan K. F., Tan E. M. Ribonucleoprotein SS-B/La belongs to a protein family with consensus sequences for RNA-binding. Nucleic Acids Res. 1989 Mar 25;17(6):2233–2244. doi: 10.1093/nar/17.6.2233. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
- Fox R. I., Luppi M., Pisa P., Kang H. I. Potential role of Epstein-Barr virus in Sjögren's syndrome and rheumatoid arthritis. J Rheumatol Suppl. 1992 Jan;32:18–24. [PubMed] [Google Scholar]
- 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]
- Holmes D. S., Quigley M. A rapid boiling method for the preparation of bacterial plasmids. Anal Biochem. 1981 Jun;114(1):193–197. doi: 10.1016/0003-2697(81)90473-5. [DOI] [PubMed] [Google Scholar]
- Kohsaka H., Yamamoto K., Fujii H., Miura H., Miyasaka N., Nishioka K., Miyamoto T. Fine epitope mapping of the human SS-B/La protein. Identification of a distinct autoepitope homologous to a viral gag polyprotein. J Clin Invest. 1990 May;85(5):1566–1574. doi: 10.1172/JCI114606. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kozak M. An analysis of vertebrate mRNA sequences: intimations of translational control. J Cell Biol. 1991 Nov;115(4):887–903. doi: 10.1083/jcb.115.4.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McNeilage L. J., Umapathysivam K., Macmillan E., Guidolin A., Whittingham S., Gordon T. Definition of a discontinuous immunodominant epitope at the NH2 terminus of the La/SS-B ribonucleoprotein autoantigen. J Clin Invest. 1992 May;89(5):1652–1656. doi: 10.1172/JCI115762. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meerovitch K., Svitkin Y. V., Lee H. S., Lejbkowicz F., Kenan D. J., Chan E. K., Agol V. I., Keene J. D., Sonenberg N. La autoantigen enhances and corrects aberrant translation of poliovirus RNA in reticulocyte lysate. J Virol. 1993 Jul;67(7):3798–3807. doi: 10.1128/jvi.67.7.3798-3807.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meilof J. F., Hebeda K. M., de Jong J., Smeenk R. J. Analysis of heavy and light chain use of lupus-associated anti-La/SS-B and anti-Sm autoantibodies reveals two distinct underlying immunoregulatory mechanisms. Res Immunol. 1992 Sep;143(7):711–720. doi: 10.1016/0923-2494(92)80009-a. [DOI] [PubMed] [Google Scholar]
- Mierendorf R. C., Percy C., Young R. A. Gene isolation by screening lambda gt11 libraries with antibodies. Methods Enzymol. 1987;152:458–469. doi: 10.1016/0076-6879(87)52054-7. [DOI] [PubMed] [Google Scholar]
- Moutsopoulos H. M., Youinou P. New developments in Sjögren's syndrome. Curr Opin Rheumatol. 1991 Oct;3(5):815–822. doi: 10.1097/00002281-199110000-00011. [DOI] [PubMed] [Google Scholar]
- Pruijn G. J., Slobbe R. L., van Venrooij W. J. Analysis of protein--RNA interactions within Ro ribonucleoprotein complexes. Nucleic Acids Res. 1991 Oct 11;19(19):5173–5180. doi: 10.1093/nar/19.19.5173. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rauh A. J., Hornig H., Lührmann R. At least three distinct B cell epitopes reside in the C-terminal half of La protein, as determined by a recombinant DNA approach. Eur J Immunol. 1988 Dec;18(12):2049–2057. doi: 10.1002/eji.1830181227. [DOI] [PubMed] [Google Scholar]
- Schreck R., Albermann K., Baeuerle P. A. Nuclear factor kappa B: an oxidative stress-responsive transcription factor of eukaryotic cells (a review). Free Radic Res Commun. 1992;17(4):221–237. doi: 10.3109/10715769209079515. [DOI] [PubMed] [Google Scholar]
- Semsei I., Ma S. Y., Cutler R. G. Tissue and age specific expression of the myc proto-oncogene family throughout the life span of the C57BL/6J mouse strain. Oncogene. 1989 Apr;4(4):465–471. [PubMed] [Google Scholar]
- Short J. M., Fernandez J. M., Sorge J. A., Huse W. D. Lambda ZAP: a bacteriophage lambda expression vector with in vivo excision properties. Nucleic Acids Res. 1988 Aug 11;16(15):7583–7600. doi: 10.1093/nar/16.15.7583. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sturgess A. D., Peterson M. G., McNeilage L. J., Whittingham S., Coppel R. L. Characteristics and epitope mapping of a cloned human autoantigen La. J Immunol. 1988 May 1;140(9):3212–3218. [PubMed] [Google Scholar]
- Talal N., Dauphinée M. J., Dang H., Alexander S. S., Hart D. J., Garry R. F. Detection of serum antibodies to retroviral proteins in patients with primary Sjögren's syndrome (autoimmune exocrinopathy). Arthritis Rheum. 1990 Jun;33(6):774–781. doi: 10.1002/art.1780330603. [DOI] [PubMed] [Google Scholar]
- 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]
