Abstract
We describe an autoantibody specificity present in a subgroup of patients with a severe form of autoimmune chronic active hepatitis. These antibodies precipitate a 90-nucleotide RNA from human whole cell extracts and recognize a 48-kDa polypeptide in immunoblotting assays. The RNA is a UGA suppressor serine tRNA that carries selenocysteine (tRNA[Ser]Sec)), as shown by sequence analysis. The protein does not appear to be seryl-tRNA synthetase; rather, it is an excellent candidate for a factor involved in cotranslational selenocysteine incorporation in human cells.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bernstein R. M., Bunn C. C., Hughes G. R., Francoeur A. M., Mathews M. B. Cellular protein and RNA antigens in autoimmune disease. Mol Biol Med. 1984 Apr;2(2):105–120. [PubMed] [Google Scholar]
- Bernstein R. M., Mathews M. B. Autoantibodies to intracellular antigens, with particular reference to transfer RNA and related proteins in myositis. J Rheumatol Suppl. 1987 Jun;14 (Suppl 13):83–88. [PubMed] [Google Scholar]
- Bunn C. C., Bernstein R. M., Mathews M. B. Autoantibodies against alanyl-tRNA synthetase and tRNAAla coexist and are associated with myositis. J Exp Med. 1986 May 1;163(5):1281–1291. doi: 10.1084/jem.163.5.1281. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Böck A., Forchhammer K., Heider J., Baron C. Selenoprotein synthesis: an expansion of the genetic code. Trends Biochem Sci. 1991 Dec;16(12):463–467. doi: 10.1016/0968-0004(91)90180-4. [DOI] [PubMed] [Google Scholar]
- Dang C. V., Dang C. V. Higher eukaryotic aminoacyl-tRNA synthetases in physiologic and pathologic states. Mol Cell Biochem. 1986 Aug;71(2):107–120. doi: 10.1007/BF00214769. [DOI] [PubMed] [Google Scholar]
- Diamond A., Dudock B., Hatfield D. Structure and properties of a bovine liver UGA suppressor serine tRNA with a tryptophan anticodon. Cell. 1981 Aug;25(2):497–506. doi: 10.1016/0092-8674(81)90068-4. [DOI] [PubMed] [Google Scholar]
- England T. E., Uhlenbeck O. C. 3'-terminal labelling of RNA with T4 RNA ligase. Nature. 1978 Oct 12;275(5680):560–561. doi: 10.1038/275560a0. [DOI] [PubMed] [Google Scholar]
- Epstein P., Lidsky M., Reddy R., Tan E., Busch H. Identification of three different anti-4S RNA sera associated with autoimmune disease. Biochem Biophys Res Commun. 1982 Nov 30;109(2):548–555. doi: 10.1016/0006-291x(82)91756-9. [DOI] [PubMed] [Google Scholar]
- Forman M. S., Nakamura M., Mimori T., Gelpi C., Hardin J. A. Detection of antibodies to small nuclear ribonucleoproteins and small cytoplasmic ribonucleoproteins using unlabeled cell extracts. Arthritis Rheum. 1985 Dec;28(12):1356–1361. doi: 10.1002/art.1780281207. [DOI] [PubMed] [Google Scholar]
- Gelpi C., Algueró A., Angeles Martinez M., Vidal S., Juarez C., Rodriguez-Sanchez J. L. Identification of protein components reactive with anti-PM/Scl autoantibodies. Clin Exp Immunol. 1990 Jul;81(1):59–64. doi: 10.1111/j.1365-2249.1990.tb05291.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hardin J. A., Rahn D. R., Shen C., Lerner M. R., Wolin S. L., Rosa M. D., Steitz J. A. Antibodies from patients with connective tissue diseases bind specific subsets of cellular RNA-protein particles. J Clin Invest. 1982 Jul;70(1):141–147. doi: 10.1172/JCI110587. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hatfield D., Diamond A., Dudock B. Opal suppressor serine tRNAs from bovine liver form phosphoseryl-tRNA. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6215–6219. doi: 10.1073/pnas.79.20.6215. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hendrick J. P., Wolin S. L., Rinke J., Lerner M. R., Steitz J. A. Ro small cytoplasmic ribonucleoproteins are a subclass of La ribonucleoproteins: further characterization of the Ro and La small ribonucleoproteins from uninfected mammalian cells. Mol Cell Biol. 1981 Dec;1(12):1138–1149. doi: 10.1128/mcb.1.12.1138. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hong H. J., Hoe K. L., Ryu C. J., Yoo O. J. An additional human serine tRNA gene. Nucleic Acids Res. 1992 Mar 11;20(5):1144–1144. doi: 10.1093/nar/20.5.1144. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hong H. J., Yoo S. H., Yoo O. J. The nucleotide sequence of a human serine tRNA gene. Nucleic Acids Res. 1987 Jun 25;15(12):4987–4987. doi: 10.1093/nar/15.12.4987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Krupp J. L., Shu H. H., Martin N. C. Human tRNASer gene organization and a tRNASer gene sequence. Nucleic Acids Res. 1988 Jan 25;16(2):770–770. doi: 10.1093/nar/16.2.770. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee B. J., Rajagopalan M., Kim Y. S., You K. H., Jacobson K. B., Hatfield D. Selenocysteine tRNA[Ser]Sec gene is ubiquitous within the animal kingdom. Mol Cell Biol. 1990 May;10(5):1940–1949. doi: 10.1128/mcb.10.5.1940. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee B. J., Worland P. J., Davis J. N., Stadtman T. C., Hatfield D. L. Identification of a selenocysteyl-tRNA(Ser) in mammalian cells that recognizes the nonsense codon, UGA. J Biol Chem. 1989 Jun 15;264(17):9724–9727. [PubMed] [Google Scholar]
- 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]
- Love L. A., Leff R. L., Fraser D. D., Targoff I. N., Dalakas M., Plotz P. H., Miller F. W. A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups. Medicine (Baltimore) 1991 Nov;70(6):360–374. doi: 10.1097/00005792-199111000-00002. [DOI] [PubMed] [Google Scholar]
- Mathews M. B., Bernstein R. M. Myositis autoantibody inhibits histidyl-tRNA synthetase: a model for autoimmunity. Nature. 1983 Jul 14;304(5922):177–179. doi: 10.1038/304177a0. [DOI] [PubMed] [Google Scholar]
- Mathews M. B., Reichlin M., Hughes G. R., Bernstein R. M. Anti-threonyl-tRNA synthetase, a second myositis-related autoantibody. J Exp Med. 1984 Aug 1;160(2):420–434. doi: 10.1084/jem.160.2.420. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matter L., Schopfer K., Wilhelm J. A., Nyffenegger T., Parisot R. F., De Robertis E. M. Molecular characterization of ribonucleoprotein antigens bound by antinuclear antibodies. A diagnostic evaluation. Arthritis Rheum. 1982 Nov;25(11):1278–1283. doi: 10.1002/art.1780251102. [DOI] [PubMed] [Google Scholar]
- Mimori T., Hinterberger M., Pettersson I., Steitz J. A. Autoantibodies to the U2 small nuclear ribonucleoprotein in a patient with scleroderma-polymyositis overlap syndrome. J Biol Chem. 1984 Jan 10;259(1):560–565. [PubMed] [Google Scholar]
- Miseta A., Woodley C. L., Greenberg J. R., Slobin L. I. Mammalian seryl-tRNA synthetase associates with mRNA in vivo and has homology to elongation factor 1 alpha. J Biol Chem. 1991 Oct 15;266(29):19158–19161. [PubMed] [Google Scholar]
- Miyachi K., Takano S., Mimori T., Yamagata H., Mita S., Matsuoka Y., Irimajiri S., Tani K., Akizuki M., Homma M. A novel autoantibody reactive with a 48 kDa tRNA associated protein in patients with scleroderma. J Rheumatol. 1991 Mar;18(3):373–378. [PubMed] [Google Scholar]
- O'Neill V. A., Eden F. C., Pratt K., Hatfield D. L. A human opal suppressor tRNA gene and pseudogene. J Biol Chem. 1985 Feb 25;260(4):2501–2508. [PubMed] [Google Scholar]
- Okada N., Mukai R., Harada F., Kabashima T., Nakao Y., Yamane K., Ohshima Y., Sakamoto K., Itoh M., Kashiwagi H. Isolation of a novel antibody, which precipitates ribonucleoprotein complex containing threonine tRNA from a patient with polymyositis. Eur J Biochem. 1984 Mar 15;139(3):425–429. doi: 10.1111/j.1432-1033.1984.tb08022.x. [DOI] [PubMed] [Google Scholar]
- Olmsted J. B. Affinity purification of antibodies from diazotized paper blots of heterogeneous protein samples. J Biol Chem. 1981 Dec 10;256(23):11955–11957. [PubMed] [Google Scholar]
- Reichlin M., Arnett F. C., Jr Multiplicity of antibodies in myositis sera. Arthritis Rheum. 1984 Oct;27(10):1150–1156. doi: 10.1002/art.1780271011. [DOI] [PubMed] [Google Scholar]
- Rosa M. D., Hendrick J. P., Jr, Lerner M. R., Steitz J. A., Reichlin M. A mammalian tRNAHis-containing antigen is recognized by the polymyositis-specific antibody anti-Jo-1. Nucleic Acids Res. 1983 Feb 11;11(3):853–870. doi: 10.1093/nar/11.3.853. [DOI] [PMC free article] [PubMed] [Google Scholar]
- STURGILL B. C., CARPENTER R. R. ANTIBODY TO RIBOSOMES IN SYSTEMIC LUPUS ERYTHEMATOSUS. Arthritis Rheum. 1965 Apr;8:213–218. doi: 10.1002/art.1780080205. [DOI] [PubMed] [Google Scholar]
- Silberklang M., Gillum A. M., RajBhandary U. L. Use of in vitro 32P labeling in the sequence analysis of nonradioactive tRNAs. Methods Enzymol. 1979;59:58–109. doi: 10.1016/0076-6879(79)59072-7. [DOI] [PubMed] [Google Scholar]
- Stefano J. E. Purified lupus antigen La recognizes an oligouridylate stretch common to the 3' termini of RNA polymerase III transcripts. Cell. 1984 Jan;36(1):145–154. doi: 10.1016/0092-8674(84)90083-7. [DOI] [PubMed] [Google Scholar]
- Targoff I. N. Autoantibodies to aminoacyl-transfer RNA synthetases for isoleucine and glycine. Two additional synthetases are antigenic in myositis. J Immunol. 1990 Mar 1;144(5):1737–1743. [PubMed] [Google Scholar]
- Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walker E. J., Treacy G. B., Jeffrey P. D. Molecular weights of mitochondrial and cytoplasmic aminoacyl-tRNA synthetases of beef liver and their complexes. Biochemistry. 1983 Apr 12;22(8):1934–1941. doi: 10.1021/bi00277a030. [DOI] [PubMed] [Google Scholar]
- 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]