The role of tandem tudor domain proteins in RNAi

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RNA-mediated interference, or RNAi, is the specific shut down of a gene's expression by the exposure of cells to double-stranded RNA, or to its derivatives. This phenomenon has had a deep impact on biological sciences in the recent years, primarily for its use to experimentally examine the outcome of the loss of any gene's function in experiments. In the most recent years it is becoming clear that RNAi also serves numerous physiological purposes. Through a diverse variety of related processes, it can profoundly influence gene regulatory networks. In the current research proposal, we put forward an integrated strategy to address the molecular basis for one of these phenomena termed endogenous RNAi (or endoRNAi). EndoRNAi modifies gene expression by converging its silencing signals on chromatin (the physiological architechtures of DNA). We will examine the function of two related proteins required for endoRNAi, which encode tandem tudor domains. Our previous work supports a model wherein these proteins direct the RNAi machinery to reinforce the silenced state of genes. The current proposal will result in a better understanding of the biological functions of RNAi, of the underlying mechanisms, and further elucidate the functions of the tudor domains in gene regulation.