Grant: Project Grant

DNA is copied into messenger RNAs (mRNAs), which in turn encode proteins. For most of the second half of the 20th Century it was thought that the regulation of which proteins are made in any particular cell of the body or stage of development is at the level of transcription (production of mRNA from DNA). However, it has become clear in the last decade that a great deal of this regulation occurs post-transcriptionally via control of mRNA stability, localization within the cell and/or in the translation of the mRNA into protein. These processes are regulated by RNA-binding proteins (RBPs), which together with their bound mRNAs and other associated proteins, regulate these processes. In order to obtain a comprehensive understanding of the molecular mechanisms of post-transcriptional control and how the compendium of proteins in each cell type is assembled, we will use the powerful model organism, the fruit fly Drosophila, to systematically identify the mRNAs bound to each of 68 RBPs in the early embryo together with other associated RNAs and proteins. We will use experimental and computational methods to identify the binding sites for each of these 68 RBPs. Finally, we will assess the molecular functions of these binding sites in control of the post-transcriptional processes listed above. Together these studies will provide the first insights into how the 'post-transcriptional code' is read out as the compendium of proteins present in a cell. Given that RBPs and their binding sites tend to be highly evolutionarily conserved and that 90% of the closely related human RBPs have been associated with a variety of diseases, our results will lead directly to insights into the components and functions of post-transcriptional processes in other organisms, including humans.