The goals of this research are to understand the mechanism of inhibition and activation of Xenopus maternal mRNA translation during meiotic maturation and early embryogenesis, and to identify trans-acting cellular factors involved in this translational control. Early frog embryogenesis depends on the regulated translation of a maternal pool of mRNA to execute critical intercellular signalling events. Fibroblast growth factor receptor-1 (FGFR), which is required for normal development, is stored as a stable, untranslated maternal mRNA transcript in the fully grown immature oocyte, but is translationally activated at meiotic maturation. Previous work in this lab has identified a 180 nucleotide cis-acting element in the FGF receptor 3' untranslated region (UTR) which inhibits translation in the immature oocyte and which is sufficient to inhibit translation of heterologous reporter mRNAs. This cis-acting regulatory element is also involved in the timing of activation of translation during meiosis, and specifically binds to oocyte cytoplasmic protein suggesting that translational repression is mediated by RNA-protein interactions. We continue this work with the following specific aims: 1) to further study the structural and functional characteristics of this 3' UTR translational control element through a complete mutational analysis and the identification of the minimal inhibitory element; 2) to identify the 43 kDa oocyte cytoplasmic 3' UTR-binding protein through biochemical purification and cDNA cloning; and 3) to characterize the 43 kDa FGFR 3'UTR- binding protein during oogenesis, oocyte meiotic maturation and early embryogenesis; and study its role in FGFR translation in oocyte extracts and a Xenopus cell transfection assay. Investigation of the molecular basis of FGF receptor translational control will bring to light mechanisms specific for translational control processes during early development and will provide new insights into the fundamental mechanisms of eukaryotic translation. These insights will ultimately aid in our understanding of the pathogenesis of congenital anomalies and malignant transformation.
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