Eukaryotic small ribonucleoproteins. Anti-La human autoantibodies react with U1 RNA-protein complexes.
Anti-La sera from patients with autoimmune disorders precipitate a set of nuclear and cytoplasmic small RNA-protein complexes. Up to now, it has been thought that the La antigen is associated only with RNAs transcribed by RNA polymerase III, including precursors of tRNA and 5 S ribosomal RNA. Here we report that anti-La sera also react with ribonucleoprotein particles containing small nuclear RNA U1, which is transcribed by RNA polymerase II. Anti-La sera from 12 out of 12 patients tested were found to precipitate U1 RNA-protein complexes from HeLa cell nuclear extracts, under conditions where nonimmune sera do not. Ribonucleoprotein particles containing a second small nuclear RNA, U2, do not react appreciably with anti-La sera although they are present in HeLa cell nuclei at the same concentration as U1 RNA. Anti-La sera also react with U1 RNA-protein complexes in mouse and frog cells, but not in Drosophila or Chironomus, two organisms which lack the La antigen. Hybridization of cloned U1 DNA with anti-La-reactive RNA from HeLa cell nuclear extracts reveals mature U1 RNA, whereas anti-La-reactive cytoplasmic RNA contains a series of hybridizing bands that represent molecules 1-7 nucleotides longer than U1 and which may include precursors of nuclear U1 RNA (Madore, S. J., Wieben, E. D., and Pederson, T. (1984) J. Cell Biol., 188-192). Pulse-chase experiments suggest that the association of La antigenicity with these cytoplasmic U1 RNA molecules is transient. These results are discussed in relation to the presence of uridylate-rich sequences in the 3' termini of U1 RNA precursors and mature U1 RNA, which are similar to La antigen binding sites in several RNAs transcribed by RNA polymerase III.
D000818:Animals; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D002460:Cell Line; D002467:Cell Nucleus / Q000032:analysis; D004330:Drosophila; D006367:HeLa Cells / Q000032:analysis; D006801:Humans; D007106:Immune Sera; D007942:Leukemia, Experimental; D051379:Mice; D009693:Nucleic Acid Hybridization; D012261:Ribonucleoproteins / Q000032:analysis* / Q000276:immunology; D017411:Ribonucleoproteins, Small Nuclear
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D007106:Immune Sera; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear