Molecular cloning of cDNA encoding Sm autoantigen: Derivation of a cDNA for a B polypeptide of the U series of small nuclear ribonucleoprotein particles

The Sm snRNPs play a central role in the processing of pre-mRNA. Anti-Sm antibodies, the diagnostic hallmark of systemic lupus erythematosus, target the B'/B and D polypeptides of these snRNPs. We have used patient autoantibodies to clone a cDNA from a human fibroblast cDNA library that encodes the full length of a polypeptide identical with, or closely related to, polypeptide B. This cDNA is comprised of 1139 bases and contains an open reading frame of 855 nucleotides that is capable of encoding 285 amino acids. The first 223 amino acids at the NH₂ terminus exhibit nearly complete homology with polypeptide N, a newly recognized brain- and heart-specific component of Sm snRNPs. The derived amino acid sequence for B differs from that of the N polypeptide primarily by a 50-amino acid insert 12 residues upstream from the homologous COOH termini of these polypeptides. The structural differences in these cDNAs for B and N may regulate tissue-specific alternative splicing mechanisms for mRNA. In addition, these clones make it possible to map in fine detail the most characteristic autoimmune responses of systemic lupus erythematosus.