hPop1: An autoantigenic protein subunit shared by the human RNase P and RNase MRP ribonucleoproteins

The eukaryotic endonucleases RNase P and RNase MRP require both RNA and protein subunits for function, Even though the human RNase P and MRP RNAs were previously characterized, the protein composition of the particles remains unknown, We have identified a human and a Caenorhabditis elegans sequence showing homology to yPop1, a protein subunit of the yeast RNase P and MRP particles. A cDNA containing the complete coding sequence for the human protein, hPop1, was cloned. Sequence analysis identifies three novel sequence motifs, conserved between the human, C.elegans and yeast proteins. Affinity-purified anti-hPop1 antibodies recognize a single 115 kDa protein in HeLa cell nuclear extracts, Immunoprecipitations with different anti-hPop1 antibodies demonstrate an association of hPop1 with the vast majority of the RNase P and MRP RNAs in HeLa cell nuclear extracts, Additionally, anti-hPop1 immunoprecipitates possess RNase P enzymatic activity, These results establish hPop1 as the first identified RNase P and MRP protein subunit from humans. Anti-hPop1 antibodies generate a strong nucleolar and a weaker homogeneous nuclear staining in HeLa cells, A certain class of autoimmune patient serum precipitates in vitro-translated hPop1, hPop1 is therefore an autoantigen in patients suffering from connective tissue diseases.