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Macromolecular machines that regulate mRNA poly(A) tails: mechanisms of polyadenylation and deadenylation (POLYAMECHANISMS)
Start date: Jan 1, 2011, End date: Dec 31, 2016 PROJECT  FINISHED 

The objective of my laboratory is to understand the mechanisms of mRNA polyadenylation and deadenylation, thereby providing fundamental insight into the regulation of eukaryotic gene expression. These objectives will be met through an integrated, multidisciplinary approach combining structural, biochemical, biophysical and yeast genetic techniques. Specifically, I propose to establish how mRNA poly(A) tail position and length are determined by the Cleavage and Polyadenylation Factor (CPF) and by the Ccr4-Not complex.Gene expression is tightly regulated, both spatially and temporally. Traditionally, this has been studied through transcription but more recent work has shown that post-transcriptional mechanisms play extensive roles. Many of these post-transcriptional functions are mediated by poly(A) tails which are found on almost all eukaryotic mRNAs. The CPF and Ccr4-Not complexes influence poly(A) tails to regulate mRNA stability and the efficiency of translation. They also mediate the periodic expression of cell cycle-related genes, microRNA-targeted gene silencing and expression of maternal masked mRNAs in oocyte development. My work will address many of these functions and will have broad-ranging biological and technological implications including: a better understanding of gene expression and the newly-emerging field of post-transcriptional regulation, the development of new technologies to study multi-protein complexes and the identification of potential therapeutic targets.

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