RNA interference in yeast

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RNA interference (RNAi) is a conserved process that uses small RNAs to control gene expression. Although it was only discovered in 1998, RNAi is an ancient process that is ubiquitous in eukaryotes. The rapid development of RNAi as a tool revolutionized the study of gene function and it holds great promise for treatment of genetic and infectious diseases in humans, animals and plants. The basic steps in RNAi are well understood and the development of RNAi as a laboratory tool has rapidly outpaced the study of cellular mechanisms that regulate this process. What is lacking therefore is a clear picture of how RNAi is temporally and spatially regulated. This is critical because in many organisms, RNAi modulates gene expression on a global level. For example, RNAi may control the expression of more than 50% of genes in some organisms. As such, RNAi itself must be highly regulated. Yeast have served as excellent genetic and cell biological model organisms for the study of complex regulatory networks. Indeed, the study of RNAi in the fission yeast Schizosaccharomyces pombe has uncovered previously unknown pathways for regulating gene expression. Unlike most other eukaryotes, Saccharomyces cerevisiae recently lost a number of key RNAi genes and until recently, researchers were not able to harness the power of this model system to study RNAi. However, we and other laboratories have been able to reconstitute yeast and mammalian RNAi pathways in S. cerevisiae. As such, budding yeast can serve as a scaffold organism with which to build up RNAi systems. The main goal of our research program is to understand the evolution of RNAi regulatory networks in yeast by identifying common and unique regulators of RNAi in fission and budding yeast. We will focus on two main areas: 1) How Argonautes and Dicer proteins functionally interact during processing and loading of small RNAs; 2) Characterization of kinases and phosphatases that regulate RNAi in yeast.