Sage Journals: Discover world-class research

Abstract

The York Avenue (New York) ‘ecosystem’from the 1940s through the 1980s enabled Henry Kunkel to apply new scientific methodology to understandinghuman disease. Stephanie Smith, a young woman with lupus, was treated at the Rockefeller University Hospital in the 1960s. Studies of her antinuclear antibodies by Kunkel and Eng Tan led to the discovery of a precipitin line specific for lupus, and the responsible antigen was designated Sm (for ‘Smith’). This review outlines the history of Sm antigen from an interesting precipitin line to the identification of small nuclear RNA molecules and small nuclear ribonucleoproteins, and subsequently the discovery of RNA splicing. The story illustrates Henry Kunkel’s approach to science, emphasizing how ‘accidental’clinical observations, in the hands of skilled investigators, can have unexpectedand potentiallymomentous implications.

Keywords

small nuclear ribonucleoproteins Sm antigen antinuclear antibodies RNA processing history of medicine

Get full access to this article

View all access options for this article.

References

Tan EM , Kunkel HG. Characteristics of a soluble nuclear antigen precipitating with sera of patients with systemic lupus erythematosus . J Immunol 1966; 96: 464-471 .

Mattioli M , Reichlin M. Characterization of a soluble nuclear ribonucleoprotein antigen reactive with SLE sera . J Immunol 1971; 107: 1281-1290 .

Mattioli M , Reichlin M. Physical association of two nuclear antigens and mutual occurrence of their antibodies: the relationship of the Sm and RNA protein (Mo) systems in SLE sera . J Immunol 1973; 110: 1318-1324 .

Reeves WH , Fisher DE , Lahita RG , Kunkel HG. Autoimmune sera reactive with Sm antigen contain high levels of RNP-like antibodies . J Clin Invest 1985; 75: 580-587 .

Conner GE , Nelson D , Wisniewolski R , Lahita RG , Blobel G , Kunkel HG. Protein antigens of the RNA-protein complexes detected by anti-Sm and anti-RNP antibodies found in serum of patients with systemic lupus erythematosus and related disorders . J Exp Med 1982; 156: 1475-1485 .

Fisher DE , Conner GE , Reeves WH , Wisniewolski R , Blobel G. Small nuclear ribonucleoprotein particle assembly in vivo: demonstration of a 6S RNA-free core precursor and posttranslational modification . Cell 1985; 42: 751-758 .

Kambach C , Walke S , Young R , Avis JM , de la FE , Raker VA et al. Crystal structures of two Sm protein complexes and their implications for the assembly of the spliceosomal snRNPs . Cell 1999; 96(3): 375-387 .

Lerner MR , Steitz JA. Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus . Proc Natl Acad Sci USA 1979; 76: 5495-5499 .

Padgett RA , Mount SM , Steitz JA , Sharp PA. Splicing of messenger RNA precursors is inhibited by antisera to small nuclear ribonucleoproteins . Cell 1983; 35: 101-107 .

10.

Padgett RA , Grabowski PJ , Konarska MM , Seiler S , Sharp PA. Splicing of messenger RNA precursors . A Rev Biochem 1986; 55: 1119-1150 .

11.

Lee SI , Steitz JA. Herpes virus saimiri U RNAs are expressed and assembled into ribonucleoprotein particles in the absence of other viral genes . J Virol 1990; 64(8): 3905-3915 .

12.

Dong X , Hamilton KJ , Satoh M , Wang J , Reeves WH. Initiation of autoimmunity to the p53 tumor suppressor protein by complexes of p53 and SV40 large T antigen . J Exp Med 1994; 179: 1243-1252 .

13.

James JA , Harley JB. Linear epitope mapping of an Sm B=B0 polypeptide . J Immunol 1992; 148: 2074-2079 .

14.

Satoh M , Langdon JJ , Hamilton KJ , Richards HB , Panka D , Eisenberg RA et al. Distinctive immune response patterns of human and murine autoimmune sera to U1 small nuclear ribonucleoprotein C protein . J Clin Invest 1996; 97: 2619-2626 .

15.

Brahms H , Raker VA , van Venrooij WJ , Luhrmann R. A major, novel systemic lupus erythematosus autoantibody class recognizes the E, F, and G Sm snRNP proteins as an E-F-G complex but not in their denatured states . Arthritis Rheum 1997; 40: 672-682 .

16.

Satoh M , Richards HB , Hamilton KJ , Reeves WH. Human anti-nRNP autoimmune sera contain a novel subset of autoantibodies that stabilizes the molecular interaction of U1RNP-C protein with the Sm core proteins . J Immunol 1997; 158: 5017-5025 .

17.

Deutscher SL , Keene JD. A sequence-specific conformational epitope on U1 RNA is recognized by a unique autoantibody . Proc Natl Acad Sci USA 1988; 85: 3299-3303 .

18.

Hoet RM , de Weerd P , Gunnewiek JK , Koornneef I , van Venrooij WJ. Epitope regions of U1 small nuclear RNA recognized by anti-U1RNA-specific autoantibodies . J Clin Invest 1992; 90: 1753-1762 .

19.

Brahms H , Raymackers J , Union A , de Keyser F , Meheus L , Luhrmann R. The C-terminal RG dipeptide repeats of the spliceosomal Sm proteins D1 and D3 contain symmetrical dimethylarginines, which form a major B-cell epitope for anti-Sm autoantibodies . J Biol Chem 2000; 275(22): 17122-17129 .

Henry Kunkel,Stephanie Smith,clinical immunology,and split genes

Abstract

Keywords

Get full access to this article

References