Community Research and Development Information Service - CORDIS

Final Activity Report Summary - CYTOPLASMIC POLYADEN (Translational control by cytoplasmic polyadenylation during the cell cycle)

The expression of many genes involved in the control of cell proliferation and differentiation is regulated, at the translation level, by sequences located in the untranslated regions of their messenger Ribonucleic acids (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 for a coordinated regulation of subgroups of genes necessary for cell cycle progress. Enhanced translation of mRNAs by cytoplasmic polyadenylation was linked to the presence of elements at the 3' end of the mRNAs where the Cytoplasmic polyadenylation element binding (CPEB) protein binds. This mechanism of translational control was shown to control oogenesis, early development and synapses activity in neurons, while some recent reports also suggest a role of cytoplasmic polyadenylation in cell cycle progression of somatic cells.

This research project addressed the role of cytoplasmic polyadenylation in coordinating gene expression during the mitotic cell cycle. By conducting a genome wide screening it was found that a population of mRNAs had a long poly(A) tail at early S phase and these mRNAs became deadenylated later on during both S and M phase, while in G1 phase they started to become polyadenylated again. The analysis of the sequences of these mRNAs should allow for 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, was also examined and it was found that CPEB1, 2 and 4 mediated translational regulation by cytoplasmic polyadenylation in xenopus oocytes.

The regulation mechanism of these CPEBs activity and factors associated to them remained to be explored. The putative CPEB protein responsible for cell cycle regulation of these mRNAs was being characterised, by the time of the project completion, and CPEBs knockdown experiments were anticipated to shed light on the impact of cell cycle progression. The final goal was to define the relevance of control of gene expression by cytoplasmic polyadenylation during the mitotic cell cycle.

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