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Our research is focused on post-transcriptional gene regulation in eukaryotes. Using the yeast Saccharomyces cerevisiae as a model, and employing a combination of genetic, molecular biology, biochemistry, genomic, and bioinformatics approaches, we seek to understand and uncover the basic mechanisms that control cytoplasmic mRNA translation and decay. Our early work addressed the function and molecular mechanisms of nonsense-mediated mRNA decay (NMD). These studies identified several key factors involved in yeast NMD and defined the substrates for this mRNA decay pathway. Our recent work addresses the molecular functions of yeast decapping factors in mRNA decapping regulation. These studies uncovered several unusual regulatory mechanisms involved in mRNA decapping, including transcript-specific regulation mediated by Edc3 and both the positive and negative regulation of the yeast decapping enzyme mediated by genetic elements located in the C-terminal domain of Dcp2. We are currently investigating the molecular mechanisms controlling the yeast decapping enzyme’s in vivo targeting and activation, and the functions of different decapping activators in mRNA decapping regulation.