REGULATED MRNA TRANSLATION IN DROSOPHILA BODY PATTERNING

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The first steps in animal development, formation of the egg and the beginning of embryogenesis, rely heavily on maternally-synthesized mRNAs. The mother provides the egg with a vast store of mRNAs to support development until the genome of the zygote becomes transcriptionally active and can assume control. Some of these mRNAs actually direct development, providing the embryo with the plans to organize the body plan, or to specify different germ layers. A crucial feature of this strategy is that the maternal mRNAs can be used only at appropriate times and places, so that each region of the embryo receives only the correct instructions. One of the most common mechanisms to control the use of maternal mRNAs involves regulated mRNA translation, and recent advances in the study of Drosophila oogenesis and early embryogenesis have shown that translational regulation play a critical role in the development of that animal. This provides the opportunity to use genetic as well as biochemical approaches to study mechanisms of translational control. We plan to use Drosophila to examine both negative and positive regulation of translation. Both forms of regulation are exerted on the oskar mRNA, a key component in the system that directs posterior body patterning in the oocyte and embryo, and much of our efforts will focus on that mRNA. oskar mRNA is translationally repressed by an ovarian protein, obp80, that binds to multiple sites in the 3' untranslated region of the mRNA. By purifying the obp80 protein and gene, we can apply genetic and biochemical approaches to ask how translational repression is accomplished. Positive control of oskar mRNA translation is provided by the aubergine gene, which is also required for translation of an mRNA (gurken) involved in dorsoventral body patterning. We will identify the features of the oskar and gurken mRNAs that make them dependent on aubergine for translation, and use this information to distinguish between different models of positive translational control. Our progress towards this goal will be aided by identifying other aubergine-dependent mRNAs, and comparing the mRNAs to recognize conserved features. We will also clone the aubergine gene. Neither positive nor negative control of translation is understood in detail, yet both types of regulation appear to be used frequently. In particular, translational regulation is a level of gene expression at which may viruses circumvent or alter host controls or machinery. Thus, our work will provide insights into mechanisms of development and of gene expression, and may ultimately provide insights that facilitate prophylactic or therapeutic solutions to viral infections.