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COMPARING THE LEVEL OF GENE EXPRESSION IN [PSI+] AND [psi-] BETWEEN DIFFERENT STRAINS OF SACCHAROMYCES CEREVISIAE. A. Khazali1, C. Alexander1, H. Amin1, S. Zimmermann1, Y.Tra2, I. M. Evans*1, 1 Department of Biological Sciences 2Department of Mathematics and Statistics [email protected], [email protected], [email protected], [email protected], [email protected], [email protected]. Proteins in their prion form are thought to be involved in spongiform neurodegenerative diseases such as Creutzfeldt-Jakob (CJ) disease commonly known as “mad cow disease”. Saccharomyces cerevisiae (yeast) provides a valuable model system to study prion proteins and their effects on cells. In S.cerevisiae, the Sup35 gene codes for a translational release factor protein (eRF3). A prion conformation of this protein will result in inefficient translation termination and cause the yeast strain to undergo phenotypic changes. The yeast strain containing the prion form of Sup35 product is designated as [PSI+], while the strain with normal Sup35 product is called [psi-]. In order to understand the effect of prions on a yeast cell, we conducted transcriptional profiling using DNA microarrays on the isogenic [PSI+] and [psi-] of S.cerevisiae (strain L1763). We found that there are a lot of retrotransposon genes that are differentially expressed in [PSI+] when compared to [psi-]. Changes in retrotransposon RNA have been shown to be involved in gene recombination and rearrangement which can give rise to genomic variation. The changes in retrotransposon RNA are interesting because there are other strains of S.cerevisiae with different genetic backgrounds and previous work done by others has suggested that [PSI+] generates different phenotypes in the different genetic backgrounds of these yeast strains. We asked the question whether the same changes in the levels of retrotransposon RNA would be found when we compared gene transcription in these different strains. For these studies we used yeast 74D [PSI+] and [psi-] strains. When comparing the gene expression of S.cerevisiae 74D and L1763, we found that only 17.12% or 269 genes are altered in their expression in both strains. Of these 269 genes, 82 genes are underexpressed and 51 genes are overexpressed in both 74D and L1763 yeast strains. The remaining 136 genes change in both strains, but the changes are in different directions. From these studies we conclude that the presence of the Sup35 gene product in its prion form does change the levels of gene transcription. The genetic background of the strain is important as some changes are found regardless of the genetic background while other changes vary depending on the genetic background. For example, in both genetic backgrounds we found different changes in the mRNA levels of retrotransposon genes. Our studies may help to explain the prior finding that [PSI+] generates different phenotypes in different genetic backgrounds. This is because there is differential gene expression in these [PSI+] yeast strains.