Role of the CSN5 subunit of Cop9 signalosome in transcription modulation of genes involved in zinc and lipid metabolism in S. cerevisiae

The ubiquitin/proteasome system (UPS) has been shown to be necessary for tight regulation of gene expression with important implications for cellular homeostasys. A key component of the UPS is the COP9 signalosome (CSN), a protein complex conservedin all eukaryotes which regulates the cullin- based E3 ubiquitin ligases. The CSN removes the ubiquitin-like modifier Nedd8 from cullin-based E3, an activity that resides in the JAMM/MPN+ domain of CSN5. In S. cerevisiae, the CSN is smaller than other eukaryotes and its subunits are not required for viability. We performed a transcriptomic analysis of a S. cerevisiae strain deleted in the CSN5 compared with its isogenic wild type strain. Data analysis showed that 183 genes were significantly modulated at least two fold in deltaCSN5 as compared with the wt strain. In particular, we found genes belong to lipid metabolism and zinc homeostasis that are repressed. In order to support a real involvement of the CSN in these functions we performed real-time RT-PCR on 11 genes to test their modulation in different CSN-deletion mutants. We also tested CSN deletion strains for phenotypic features related to defects in zinc uptake and ergosterol biosynthesis. We are now trying to define the mechanism of this regulatory activity by proposing both an individual promoter-focused analysis and a genomic-wide proteomic approach.