The role of MAC1 in copper tolerance of Saccharomyces cerevisiae nonsense-mediated mRNA decay mutants

The nonsense-mediated mRNA (NMD) pathway, present in most eukaryotic cells is a specialized pathway that leads to the recognition and rapid degradation of mRNAs with premature termination codons and some natural mRNAs. The regulation of natural mRNAs by NMD has been observed in organisms ranging from yeast to humans. Global expression profiling of the effect of NMD on mRNA levels in Saccharomyces cerevisiae, Drosophila melanogaster and humans show that approximately 10% of the transcriptome is affected when NMD is inactivated. The regulation of natural mRNAs by NMD has been most extensively studied in S. cerevisiae and has been shown to have physiological consequences. We have shown that nmd mutants tolerate higher copper concentrations relative to wild-type yeast cells. The tolerance to high copper levels by nmd mutants is dependent on the presence of CTR2. CTR2 encodes a copper transporter of the vacuolar membrane that controls the flux of copper into the vacuole and is regulated by the NMD pathway in S. cerevisiae. Additional genes involved in copper metabolism in S. cerevisiae are also regulated by NMD. One of these genes is MAC1. The MAC1 gene in S. cerevisiae is a copper-sensing transcription factor involved in the regulation of genes that are required for high affinity copper transport. In this research, we investigated whether the NMD pathway regulates MAC1 and the role that MAC1 plays in the copper tolerance of yeast cells.