Nociceptor Sensitivity In Drosophila Melanogaster Larvae Is Controlled By RNA-Binding Proteins

Currently, there are significant gaps in understanding of the regulatory mechanisms involved in nociceptor sensitivity. Dysregulated nociceptor sensitivity is the likely pathogenesis in many types of chronic pain, a disease that ails over 100 million people in the United States alone. To improve current chronic pain therapies, it is essential to define the regulatory mechanisms responsible for nociception. The goal of this study was to characterize how genes classically involved in RNA processing and translation regulate nociceptor sensitivity. The model organism Drosophila melanogaster was used for this study because of their quantifiable response to noxious stimuli and the powerful tools available for genetic manipulations. My results suggest that eukaryotic initiation factors (eIFs) and components of the exon junction complex (EJC) control nociceptor sensitivity by regulating RNA processing and translation, suggesting a major role for RNA metabolism and translation in controlling nociceptor function. Nociceptor-specific knockdown of EJC factors and eIFs resulted in defective thermal and mechanical nociception. No direct link was found between nociceptor dendritic morphology and nociception defects, which indicates that nociceptor morphology does not determine nociceptor sensitivity. Thus, the major findings of this project revealed that Drosophila nociceptor sensitivity is controlled by RNA processing mechanisms from transcription to translation.