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 division
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 proteins that play important
roles in signal transduction, cell cycle progression, splicing,
transcription, and development.
In this report, we describe the identification of human,
nematode, and fission yeast homologues of the PRP17/CDC40
gene of S. cerevisiae. The newly identified proteins
share homology with the budding yeast protein throughout
their entire sequence, with the similarity being greatest
in the C-terminal 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
proteins co-precipitate the intron–exon 2 lariat
intermediate and the intron lariat product, providing evidence
that these proteins are spliceosome-associated. These results
show the functional conservation of the Prp17 proteins
in evolution and suggest that the second step of splicing
takes place by a similar mechanism throughout eukaryotes.