Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus

Abstract

Patients with systemic lupus erythematosus often possess antibodies against two nuclear antigens called Sm and RNP (ribonucleoprotein). We have established the molecular identity of these antigens by analyzing immune precipitates of nuclear extracts from mouse Ehrlich ascites cells labeled with 32 P and 35 S. Anti-Sm serum selectively precipitates six small nuclear RNA molecules (snRNAs); anti-RNP serum reacts with only two of these; and a third serum, characterized as mostly anti-RNP, precipitates a subset of three snRNA bands. Three of the six RNAs are identified by fingerprint analysis as the previously characterized and highly abundant nucleoplasmic snRNA species U1a (171 nucleotides), U1b, and U2 (196 nucleotides). The other three RNAs (U4, U5, and U6) likewise are uridine rich and contain modified nucleotides, but they are smaller, with lengths of about 145, 120, and 95 residues, respectively. Each of the six snRNAs is complexed with and apparently antigenic by virtue of association with specific proteins. All three sera precipitate an identical complement of seven different polypeptides ranging in molecular weight from 12,000 to 35,000; these proteins are abundant in nuclear extracts, but are neither histones nor the major polypeptides comprising the 30S heterogeneous nuclear RNP particles of mammalian nuclei. Our data argue that each of the six snRNAs exists in a separate small nuclear ribonucleoprotein (snRNP) complex with a total molecular weight of about 175,000. We find that human antisera also precipitate snRNAs from a wide range of vertebrate species and from arthropods. We discuss the antigenic snRNPs in relation to the published literature on snRNAs and nuclear RNPs and consider possible functions of snRNPs in nuclear processes.