Functional mapping of Saccharomyces cerevisiae Prp45 identifies the SNW domain as essential for viability.
The essential gene product Prp45 (379 aa) of Saccharomyces cerevisiae is a highly conserved, but N-terminally abridged, ortholog of the human transcriptional coactivator SKIP, which is involved in TGFbeta, Notch, and steroid hormone signaling. We used a diploid strain harboring PRP45 deletion, which is inviable in the haploid, to test for complementation with the truncated versions of Prp45. The N-terminal half of the protein (aa 1 to 190), denoted as the SNW domain, was found sufficient to support the essential function. Interestingly, substituting the SNW motif itself with AAA was compatible with viability. GFP-tagged Prp45 was localized in nuclear "speckles" over a diffuse nuclear background. We further found that Prp45 activated the transcription of a reporter gene in S. cerevisiae when targeted to DNA. The observed effect relied in part upon the presence of conserved helical repeats and upon the highly charged C-terminal domain (pI = 11.3). Prp45, which lacks most of the binding motifs of the human ortholog, and whose N-terminal half is sufficient for supporting the growth of prp45 cells, might be helpful in elucidating the essential function of SNW/SKIP proteins.[1]References
- Functional mapping of Saccharomyces cerevisiae Prp45 identifies the SNW domain as essential for viability. Martinkova, K., Lebduska, P., Skruzny, M., Folk, P., Puta, F. J. Biochem. (2002) [Pubmed]
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