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Human transcription co-regulator SNW1/SKIP modulates the activity of various transcription factors, the elongating complex of RNA-PolII, and the spliceosome, which suggests that SNW1/SKIP may link pre-mRNA splicing to other processes of gene expression. We identified temperature sensitive alleles of the yeast homolog of SNW1/SKIP, PRP45, which at permissive temperature elicit cell shape and cell division defects. Cwc2-TAP purified spliceosomal complexes from prp45(1-169) cells showed a decreased stoichiometry of Prp22, suggesting an aberrant association of the helicase with the spliceosome. Using a synthetic lethality screen, we isolated several alleles of PRP22 which genetically interact with the allele prp45(1-169). Splicing analysis in vivo showed that prp45(1-169) cells were less efficient in splicing of non-canonical substrates as compared to WT. The expression of Prp45(119-379) in prp45(1-169) cells restored Prp22 partition in the Cwc2-pulldowns and the splicing defects of prp45(1-169) strain. Data on splicing phenotypes of prp22 and prp45 alleles suggest that Prp45 co-modulates Prp22 in the spliceosome, contributing to splicing efficiency and proper stringency of splice site choice. This work was supported by the Czech Ministry of Education, Youth and Sports grants MSM0021620858 and LC07032. [ABSTRACT FROM AUTHOR]