Prp45p is a spliceosomal protein that plays a role in the second step of splicing. While its deletion does not affect splicing of introns that match the canonical splice site consensus sequences, it is needed for the splicing of introns with non-canonical 5', branch point, or 3' splice consensus sites (5). It is found in association with several members of the Prp19-associated NineTeen Complex (NTC) (6, 7, 5). Prp45p, like NineTeen Complex members, is also found in forms of the spliceosome containing the U2, U5, and U6 snRNPs, which are the catalytic forms of the spliceosome (1, 6, 8). Strains deleted for PRP45 are inviable (2) and depletion of Prp45p results in accumulation of unspliced precursor RNAs (1). A temperature sensitive allele of prp45 is synthetically lethal with alleles of several second step splicing factors (SLU7, PRP17, PRP18, and PRP22) and with several NTC components (SYF1, CLF1, NTC20, and CEF1; 5). Prp45p undergoes sumoylation and is a substrate of the SUMO E3 ligase Siz1p (9, 10).

PRP45 is an ortholog of the human SKIP protein which is highly conserved across eukaryotes and which is essential in C. elegans and S. pombe, as well as in S. cerevisiae. In humans, SKIP is characterized as a transcriptional coactivator acting on several signaling pathways, but more recently it has also been shown to colocalize with spliceosomes and can complement a prp45 null mutation in S. cerevisiae, suggesting that it plays a dual role (4 and refs therein). However, while Prp45p can activate expression of a reporter gene when fused to a DNA-binding domain (3), it is considered to be solely a splicing protein in S. cerevisiae (5). The fact that the sequence of Prp45p from S. cerevisiae is shorter and more diverged from the consensus than those of its orthologs, completely lacking a conserved proline-rich domain present in other species, may explain this difference in the function between S. cerevisiae Prp45p and the human SKIP protein (4, 11).

Last updated: 2009-12-01