Human RNaseP RNA and nucleolar 7-2 RNA share conserved 'To' antigen-binding domains.

RNase P in both prokaryotes and eukaryotes is a ribonucleoprotein that cleaves tRNA precursors to generate the 5' termini of the mature tRNAs. Many patients with autoimmune diseases produce antibodies against a 40 kDa protein (designated To or Th antigen) which is an integral component of eukaryotic RNaseP as well as nucleolar 7-2 RNP which is identical to the mitochondrial RNA processing (MRP) RNP. Interestingly, the To antigen found in human cells and the C5 protein, the only protein component of E. coli RNaseP, are antigenically related. In this study, we show that a 56 nucleotide-long sequence, corresponding to nucleotides 20-75 near the 5' end of human RNaseP RNA, is sufficient to bind the To antigen. We previously showed that the human To antigen binds to a short distinct structural domain near the 5' end of human 7-2/MRP RNA. There is no obvious primary sequence homology between the To antigen binding sites in RNaseP RNA and 7-2/MRP RNA; however, these sequences are capable of assuming a similar secondary structure which corresponds to the recently proposed 'cage' structure for RNaseP RNAs and 7-2/MRP RNA (Forster and Altman (1989) Cell 62: 407-409). These data are supportive of the idea that these two RNAs may have evolved from a common progenitor molecule.