The primary interest of our group is understanding the molecular mechanisms that control the temporal and spatial translation of mRNAs during the cell cycle progression and early embryonic development. Early development is programmed, at least in part, by maternally inherited mRNAs. These mRNAs are not translated en masse at any one time, or even at any one place - rather, their translation is specifically regulated by sequences located at the 3´untranslated region (3´-UTR)of the mRNA and their binding proteins. Cytoplasmic polyadenylation is one the most important mechanism for regulating translation during meiotic progresion. We take a biochemical and molecular biological approach to identify the sequences and factors that control polyadenylation-induced translation in Xenopus oocytes.

The knowledge of the molecular mechanisms that govern translational control during meiotic progression will then be applied to other mRNAs such as the one encoding for tumor suppresor p53 and its translational activation in response to DNA damage. Failure to properly regulate p53 mRNA translation results in the differentiation block and neoplastic proliferation of immature myeloid cells characteristic of the acute myeloid leukaemia.

Research Projects:

The regulated translation of messenger RNA is essential for cell cycle progression, establishment of the body plan in early development and for modulating key activities such as synaptic plasticity. Translation of especific mRNAs is often regulated by trans-acting factors that bind to specific sequences in the 3´- untranslated region of the mRNAs (3´-UTR) acting as specific repressors or activators of the translation initiation.
Cytoplasmic polyadenylation, which is one mechanism that appears to control translation in those biological theatres, is driven by CPEB, a highly conserved sequence-specific RNA binding protein that also modulates translational repression and mRNA localization (Fig 1). Our laboratory is currently focused in two biological problems that are regulated by 3´UTR-mediated translational control of specific mRNAs.