The expression of many genes involved in the control of cell proliferation and differentiation is regulated at the level of translation by sequences located in the untranslated regions of their mRNAs. These sequences act as translational repressors under normal conditions, and as translational activators in response to several stimuli. The presence of specific sequences in a subpopulation of cell mRNAs allows a coordinated regulation of subgroups of genes necessary for cell cycle progress. Enhanced translation of mRNAs by cytoplasmic polyadenylation has been linked to the presence of elements at the 3¿ end of the mRNAs where the protein CPEB binds. This mechanism of translational control has been shown to control oogenesis, early development and synapses activity in neurons, and some recent reports also suggest a role of cytoplasmic polyadenylation in cell cycle progression of somatic cells. This research project proposes to explore the role of cytoplasmic polyadenylation in coordinating gene expression during the cell cycle. The poly(A) tail of a few mRNAs known to participate in cell cycle progression will be examined to establish if cytoplasmic polyadenylation takes place at specific times of the cell cycle. In addition a functional genetic screening will be conducted to isolate genes whose poly(A) tails are polyadenylated at specific phases of the cell cycle. Analysis of the mRNAs encoded by these genes should allow the identification of cytoplasmic polyadenylation elements (CPE) and other putative regulatory elements important for the cell cycle dependent polyadenylation.The activity of factors associated to these elements, such as CPEB, will also be examined. The final goal is to advance the knowledge of control of gene expression during the cell cycle.
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