The molecular regulation of Hox gene RNA processing duringudDrosophila embryonic development

摘要

The Hox genes encode a family of developmental regulators that are essentialudfor the normal patterning of the animal body axis. Their correct expression is controlledudby a number of mechanisms including RNA processing, a molecular systemudthat allows the formation of alternative mRNAs from a single gene. Previous work inudthe Alonso Lab has demonstrated that RNA processing of the Drosophila Hox geneudUltrabithorax (Ubx) by means of alternative splicing and alternative polyadenylationudplays an important role during Drosophila development, but the mechanismsudunderlying these regulatory processes are not well understood. In this project weudfound that the Drosophila neural RNA binding protein ELAV has an important roleudin the control of both Ubx alternative splicing and polyadenylation during embryonicuddevelopment. Furthermore, by conducting a series of in vitro experiments weuddemonstrate that ELAV is able to interact with two specific RNA elements locatedudwithin Ubx intronic sequences and mutation of such elements abolishes the interaction.udWe also establish that embryos carrying a loss of function mutation in the elavudgene produce lower levels of Ubx mRNA and protein suggesting a role of ELAV onudHox gene expression. Finally we investigated the roles that other Drosophila factorsudincluding RNA binding proteins, chromatin regulators and splicing regulatoryudproteins may have on Ubx RNA processing and found several potential regulators.udAll in all our work contributes to the understanding of the molecular basis of HoxudRNA processing control during Drosophila development.