Grant: Operating Grant

Some proteins are needed all over the cell, but others need to be expressed only at a specific site within the cell. Cells can achieve local synthesis of proteins by transporting and localizing mRNA to a specific site. This process plays an important role in the development of multicellular organisms, in cell motility and in neuronal growth. Defects in the localization pathway or local translation of specific mRNAs are linked to increased cancer cell motility and neurological diseases, such as Fragile X syndrome and motor neurons disorders, so understanding this process is medically relevant. Our research aims at identifying the mechanism of action of various factors involved in the assembly and regulation of the mRNA localization and translational control machineries. It is important for the synthesis of proteins to be inhibited until the mRNA reaches its final destination so that proteins are made only where the cell needs them. We are using the budding yeast as a model system for studying these mechanisms, as several mRNAs are known to be sorted and locally translated at the bud tip of yeast cells. Furthermore, key factors involved in this process in yeast have homologs in human. This is an organism of choice for the characterization of molecular processes because of the multiple genetic, cellular and molecular biology tools available. In this proposal, we will investigate the coupling between the mRNA localization and translational control machineries during their recruitment on nascent localized transcripts. Moreover, we will study the role of post-translational modifications in the regulation of the localization process during the cell cycle and in the local activation of protein synthesis, when mRNAs reach their destination. This grant will support our continuing effort to characterize the localization and translational control machineries, and explore their role in the spatio-temporal regulation of mRNA translation.