Skip to main content
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1989 Mar 25;17(6):2233–2244. doi: 10.1093/nar/17.6.2233

Ribonucleoprotein SS-B/La belongs to a protein family with consensus sequences for RNA-binding.

E K Chan 1, K F Sullivan 1, E M Tan 1
PMCID: PMC317593  PMID: 2468131

Abstract

Autoantibodies from systemic rheumatic disorders have become useful reagents in molecular biology. SS-B/La, a major target of autoantibodies in lupus and Sjogren's syndrome, has been identified as a 46 kDa protein component of a ribonucleoprotein (RNP) particle implicated in the maturation of RNA polymerase III transcripts. This report describes the complete sequences of human and bovine SS-B/La and the identification of RNA-binding protein consensus sequences RNP1 and RNP2 in the N-terminal region previously shown to be complexed with RNA in UV-crosslinking experiments. Segments of about 95 residues from the RNA-binding domain of SS-B/La and from 29 RNA-binding domains of several other proteins are analysed with respect to the frequency of amino acids and their hydrophobicity at each position. The data suggest that SS-B/La belongs to a large family of RNA-binding proteins which includes heterogeneous nuclear RNPs, nucleolin, mRNA polyadenylate binding protein, and small nuclear RNPs.

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.

  1. Adam S. A., Nakagawa T., Swanson M. S., Woodruff T. K., Dreyfuss G. mRNA polyadenylate-binding protein: gene isolation and sequencing and identification of a ribonucleoprotein consensus sequence. Mol Cell Biol. 1986 Aug;6(8):2932–2943. doi: 10.1128/mcb.6.8.2932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alspaugh M. A., Talal N., Tan E. M. Differentiation and characterization of autoantibodies and their antigens in Sjögren's syndrome. Arthritis Rheum. 1976 Mar-Apr;19(2):216–222. doi: 10.1002/art.1780190214. [DOI] [PubMed] [Google Scholar]
  3. Bach M., Palau J. SS-B (La) nuclear antigen. Organization in structural domains of the protein moiety. Eur J Biochem. 1987 May 15;165(1):117–123. doi: 10.1111/j.1432-1033.1987.tb11201.x. [DOI] [PubMed] [Google Scholar]
  4. Bourbon H. M., Lapeyre B., Amalric F. Structure of the mouse nucleolin gene. The complete sequence reveals that each RNA binding domain is encoded by two independent exons. J Mol Biol. 1988 Apr 20;200(4):627–638. doi: 10.1016/0022-2836(88)90476-7. [DOI] [PubMed] [Google Scholar]
  5. Bugler B., Bourbon H., Lapeyre B., Wallace M. O., Chang J. H., Amalric F., Olson M. O. RNA binding fragments from nucleolin contain the ribonucleoprotein consensus sequence. J Biol Chem. 1987 Aug 15;262(23):10922–10925. [PubMed] [Google Scholar]
  6. Buvoli M., Biamonti G., Tsoulfas P., Bassi M. T., Ghetti A., Riva S., Morandi C. cDNA cloning of human hnRNP protein A1 reveals the existence of multiple mRNA isoforms. Nucleic Acids Res. 1988 May 11;16(9):3751–3770. doi: 10.1093/nar/16.9.3751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Chambers J. C., Kurilla M. G., Keene J. D. Association between the 7 S RNA and the lupus La protein varies among cell types. J Biol Chem. 1983 Oct 10;258(19):11438–11441. [PubMed] [Google Scholar]
  10. Chan E. K., Francoeur A. M., Tan E. M. Epitopes, structural domains, and asymmetry of amino acid residues in SS-B/La nuclear protein. J Immunol. 1986 May 15;136(10):3744–3749. [PubMed] [Google Scholar]
  11. Chan E. K., Tan E. M. Human autoantibody-reactive epitopes of SS-B/La are highly conserved in comparison with epitopes recognized by murine monoclonal antibodies. J Exp Med. 1987 Dec 1;166(6):1627–1640. doi: 10.1084/jem.166.6.1627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chan E. K., Tan E. M. The small nuclear ribonucleoprotein SS-B/La binds RNA with a conserved protease-resistant domain of 28 kilodaltons. Mol Cell Biol. 1987 Jul;7(7):2588–2591. doi: 10.1128/mcb.7.7.2588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Chen E. Y., Seeburg P. H. Supercoil sequencing: a fast and simple method for sequencing plasmid DNA. DNA. 1985 Apr;4(2):165–170. doi: 10.1089/dna.1985.4.165. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Chou P. Y., Fasman G. D. Prediction of the secondary structure of proteins from their amino acid sequence. Adv Enzymol Relat Areas Mol Biol. 1978;47:45–148. doi: 10.1002/9780470122921.ch2. [DOI] [PubMed] [Google Scholar]
  16. Cobianchi F., SenGupta D. N., Zmudzka B. Z., Wilson S. H. Structure of rodent helix-destabilizing protein revealed by cDNA cloning. J Biol Chem. 1986 Mar 15;261(8):3536–3543. [PubMed] [Google Scholar]
  17. Dreyfuss G., Swanson M. S., Piñol-Roma S. Heterogeneous nuclear ribonucleoprotein particles and the pathway of mRNA formation. Trends Biochem Sci. 1988 Mar;13(3):86–91. doi: 10.1016/0968-0004(88)90046-1. [DOI] [PubMed] [Google Scholar]
  18. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  19. Fox R. I., Bumol T., Fantozzi R., Bone R., Schreiber R. Expression of histocompatibility antigen HLA-DR by salivary gland epithelial cells in Sjögren's syndrome. Arthritis Rheum. 1986 Sep;29(9):1105–1111. doi: 10.1002/art.1780290908. [DOI] [PubMed] [Google Scholar]
  20. Francoeur A. M., Mathews M. B. Interaction between VA RNA and the lupus antigen La: formation of a ribonucleoprotein particle in vitro. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6772–6776. doi: 10.1073/pnas.79.22.6772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Garnier J., Osguthorpe D. J., Robson B. Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. J Mol Biol. 1978 Mar 25;120(1):97–120. doi: 10.1016/0022-2836(78)90297-8. [DOI] [PubMed] [Google Scholar]
  22. Grange T., de Sa C. M., Oddos J., Pictet R. Human mRNA polyadenylate binding protein: evolutionary conservation of a nucleic acid binding motif. Nucleic Acids Res. 1987 Jun 25;15(12):4771–4787. doi: 10.1093/nar/15.12.4771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Habets W. J., Sillekens P. T., Hoet M. H., Schalken J. A., Roebroek A. J., Leunissen J. A., van de Ven W. J., van Venrooij W. J. Analysis of a cDNA clone expressing a human autoimmune antigen: full-length sequence of the U2 small nuclear RNA-associated B" antigen. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2421–2425. doi: 10.1073/pnas.84.8.2421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Haynes S. R., Rebbert M. L., Mozer B. A., Forquignon F., Dawid I. B. pen repeat sequences are GGN clusters and encode a glycine-rich domain in a Drosophila cDNA homologous to the rat helix destabilizing protein. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1819–1823. doi: 10.1073/pnas.84.7.1819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hewick R. M., Hunkapiller M. W., Hood L. E., Dreyer W. J. A gas-liquid solid phase peptide and protein sequenator. J Biol Chem. 1981 Aug 10;256(15):7990–7997. [PubMed] [Google Scholar]
  26. Hunkapiller M. W., Lujan E., Ostrander F., Hood L. E. Isolation of microgram quantities of proteins from polyacrylamide gels for amino acid sequence analysis. Methods Enzymol. 1983;91:227–236. doi: 10.1016/s0076-6879(83)91019-4. [DOI] [PubMed] [Google Scholar]
  27. Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987 Oct 26;15(20):8125–8148. doi: 10.1093/nar/15.20.8125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lahiri D. K., Thomas J. O. A cDNA clone of the hnRNP C proteins and its homology with the single-stranded DNA binding protein UP2. Nucleic Acids Res. 1986 May 27;14(10):4077–4094. doi: 10.1093/nar/14.10.4077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Madore S. J., Wieben E. D., Pederson T. Eukaryotic small ribonucleoproteins. Anti-La human autoantibodies react with U1 RNA-protein complexes. J Biol Chem. 1984 Feb 10;259(3):1929–1933. [PubMed] [Google Scholar]
  31. Mathews M. B., Francoeur A. M. La antigen recognizes and binds to the 3'-oligouridylate tail of a small RNA. Mol Cell Biol. 1984 Jun;4(6):1134–1140. doi: 10.1128/mcb.4.6.1134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Mattioli M., Reichlin M. Heterogeneity of RNA protein antigens reactive with sera of patients with systemic lupus erythematosus. Description of a cytoplasmic nonribosomal antigen. Arthritis Rheum. 1974 Jul-Aug;17(4):421–429. doi: 10.1002/art.1780170413. [DOI] [PubMed] [Google Scholar]
  33. Merrill B. M., Stone K. L., Cobianchi F., Wilson S. H., Williams K. R. Phenylalanines that are conserved among several RNA-binding proteins form part of a nucleic acid-binding pocket in the A1 heterogeneous nuclear ribonucleoprotein. J Biol Chem. 1988 Mar 5;263(7):3307–3313. [PubMed] [Google Scholar]
  34. Needleman S. B., Wunsch C. D. A general method applicable to the search for similarities in the amino acid sequence of two proteins. J Mol Biol. 1970 Mar;48(3):443–453. doi: 10.1016/0022-2836(70)90057-4. [DOI] [PubMed] [Google Scholar]
  35. Reddy R., Henning D., Tan E., Busch H. Identification of a La protein binding site in a RNA polymerase III transcript (4.5 I RNA). J Biol Chem. 1983 Jul 10;258(13):8352–8356. [PubMed] [Google Scholar]
  36. Rinke J., Steitz J. A. Association of the lupus antigen La with a subset of U6 snRNA molecules. Nucleic Acids Res. 1985 Apr 11;13(7):2617–2629. doi: 10.1093/nar/13.7.2617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Rinke J., Steitz J. A. Precursor molecules of both human 5S ribosomal RNA and transfer RNAs are bound by a cellular protein reactive with anti-La lupus antibodies. Cell. 1982 May;29(1):149–159. doi: 10.1016/0092-8674(82)90099-x. [DOI] [PubMed] [Google Scholar]
  38. Rogers S., Wells R., Rechsteiner M. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science. 1986 Oct 17;234(4774):364–368. doi: 10.1126/science.2876518. [DOI] [PubMed] [Google Scholar]
  39. Sachs A. B., Bond M. W., Kornberg R. D. A single gene from yeast for both nuclear and cytoplasmic polyadenylate-binding proteins: domain structure and expression. Cell. 1986 Jun 20;45(6):827–835. doi: 10.1016/0092-8674(86)90557-x. [DOI] [PubMed] [Google Scholar]
  40. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  41. Sillekens P. T., Habets W. J., Beijer R. P., van Venrooij W. J. cDNA cloning of the human U1 snRNA-associated A protein: extensive homology between U1 and U2 snRNP-specific proteins. EMBO J. 1987 Dec 1;6(12):3841–3848. doi: 10.1002/j.1460-2075.1987.tb02721.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. 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]
  43. 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]
  44. Swanson M. S., Nakagawa T. Y., LeVan K., Dreyfuss G. Primary structure of human nuclear ribonucleoprotein particle C proteins: conservation of sequence and domain structures in heterogeneous nuclear RNA, mRNA, and pre-rRNA-binding proteins. Mol Cell Biol. 1987 May;7(5):1731–1739. doi: 10.1128/mcb.7.5.1731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Sweet R. M., Eisenberg D. Correlation of sequence hydrophobicities measures similarity in three-dimensional protein structure. J Mol Biol. 1983 Dec 25;171(4):479–488. doi: 10.1016/0022-2836(83)90041-4. [DOI] [PubMed] [Google Scholar]
  46. Theissen H., Etzerodt M., Reuter R., Schneider C., Lottspeich F., Argos P., Lührmann R., Philipson L. Cloning of the human cDNA for the U1 RNA-associated 70K protein. EMBO J. 1986 Dec 1;5(12):3209–3217. doi: 10.1002/j.1460-2075.1986.tb04631.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Wieben E. D., Rohleder A. M., Nenninger J. M., Pederson T. cDNA cloning of a human autoimmune nuclear ribonucleoprotein antigen. Proc Natl Acad Sci U S A. 1985 Dec;82(23):7914–7918. doi: 10.1073/pnas.82.23.7914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Wilusz J., Kurilla M. G., Keene J. D. A host protein (La) binds to a unique species of minus-sense leader RNA during replication of vesicular stomatitis virus. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5827–5831. doi: 10.1073/pnas.80.19.5827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Wu T. T., Kabat E. A. An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity. J Exp Med. 1970 Aug 1;132(2):211–250. doi: 10.1084/jem.132.2.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Young R. A., Davis R. W. Yeast RNA polymerase II genes: isolation with antibody probes. Science. 1983 Nov 18;222(4625):778–782. doi: 10.1126/science.6356359. [DOI] [PubMed] [Google Scholar]

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

RESOURCES