Autoantibodies specific for U1 RNA and initiator methionine tRNA

Autoantibodies reactive with specific nuclear and cytoplasmic small RNAs were identified by immunoprecipitation of HeLa cell RNA. Approximately 30% of antisera examined from patients with autoimmune disorders contained anti-RNA antibodies. Two previously undescribed specificities--anti U1 RNA and anti-initiator methionine tRNA--were identified. Anti-RNA antibodies were reactive with gel-purified species as well as with RNA synthesized in vitro using the SP-6 transcription system. Antigenic mapping using two sera specific for the human initiator methionine tRNA revealed separate epitopes, one of which is conserved in formyl-methionine initiator tRNA from Escherichia coli. RNA fragmentation studies further suggested that secondary or tertiary tRNA structure is required for antibody recognition. The mammalian U1 RNA specific antibodies did not precipitate small RNAs of yeast but were highly reactive with yeast ribosomal RNA, thus indicating a possible relationship between these RNA species. Results obtained with these antisera are discussed in terms of higher order structure of small RNA molecules as well as the role of nucleic acid antibodies in the autoimmune phenomenon.