The molecular regulation of Hox gene RNA processing during Drosophila embryonic development

The Hox genes encode a family of developmental regulators that are essential for the normal patterning of the animal body axis. Their correct expression is controlled by a number of mechanisms including RNA processing, a molecular system that allows the formation of alternative mRNAs from a single gene. Previous work in the Alonso Lab has demonstrated that RNA processing of the Drosophila Hox gene Ultrabithorax (Ubx) by means of alternative splicing and alternative polyadenylation plays an important role during Drosophila development, but the mechanisms underlying these regulatory processes are not well understood. In this project we found that the Drosophila neural RNA binding protein ELAV has an important role in the control of both Ubx alternative splicing and polyadenylation during embryonic development. Furthermore, by conducting a series of in vitro experiments we demonstrate that ELAV is able to interact with two specific RNA elements located within Ubx intronic sequences and mutation of such elements abolishes the interaction. We also establish that embryos carrying a loss of function mutation in the elav gene produce lower levels of Ubx mRNA and protein suggesting a role of ELAV on Hox gene expression. Finally we investigated the roles that other Drosophila factors including RNA binding proteins, chromatin regulators and splicing regulatory proteins may have on Ubx RNA processing and found several potential regulators. All in all our work contributes to the understanding of the molecular basis of Hox RNA processing control during Drosophila development.