IDENTIFICATION AND FUNCTIONAL-ANALYSIS OF HPRP17, THE HUMAN HOMOLOG OF THE PRP17 CDC40 YEAST GENE INVOLVED IN SPLICING AND CELL-CYCLE CONTROL/

The PRP17 gene of the yeast Saccharomyces cerevisiae encodes a protein that participates in the second step of the splicing reaction. It was found recently that the yeast PRP17 gene is identical to the cell div ision cycle CDC40 gene. The PRP17/CDC40 gene codes for a protein with several copies of the WD repeat, a motif found in a large family of pr oteins that play important roles in signal transduction, cell cycle pr ogression, splicing, transcription, and development, in this report, w e describe the identification of human, nematode, and fission yeast ho mologues of the PRP17/CDC40 gene of S. cerevisiae. The newly identifie d proteins share homology with the budding yeast protein throughout th eir entire sequence, with the similarity being greatest in the C-termi nal two thirds that includes the conserved WD repeats. We show that a yeast-human chimera, carrying the C-terminal two thirds of the hPRP17 protein, is able to complement the cell cycle and splicing defects of a yeast prp17 mutant, Moreover, the yeast and yeast-human chimeric pro teins co-precipitate the intron-exon 2 lariat intermediate and the int ron lariat product, providing evidence that these proteins are spliceo some-associated. These results show the functional conservation of the Prp17 proteins in evolution and suggest that the second step of splic ing takes place by a similar mechanism throughout eukaryotes.