The PRP45 gene has been identified as encoding a protein involved in mRNA splicing that is essential in Saccharomyces cerevisiae. PRP45's human homolog SKIP has been identified as a mediator of transcriptional programming in a variety of signal transduction pathways including TGFbeta, nuclear hormones, Notch, and retinoblastoma signaling. However, Skip has been also identified in purified spliceosomal complexes but an explicit role in splicing has not been identified in mammalian cells. To determine if the Skip protein could function as a splicing factor we investigated if the SKIP gene could functionally complement the yeast PRP45 gene. We show that SKIP complements the PRP45 deletion and rescues the lethal phenotype. These results show that the human SKIP gene can functionally substitute for the mRNA splicing gene PRP45 of S. cerevisiae.