The Role of RNA-Binding Protein, Pumilio, in the Regulation of Nociception

Chronic pain can be caused by gene expression changes in nociceptors that lead to pain hypersensitivity. RNA-binding proteins (RBPs) play a key role in translational control of gene expression by binding mRNA and either promoting or limiting processes such as the transport, splicing regulation, translation, and decay of mRNA. The RNA-binding protein, Pumilio, has critical roles in embryogenesis, germ cell formation, and nervous system development. Research into the roles of this RBP in motor neurons has revealed that Pum limits their excitability by repressing the translation of the voltage-gated sodium channel, Para; an ion-channel necessary for action potentials. Due to its broad roles as a translational repressor and its ability to limit neuron excitability it was hypothesized that Pum may act similarly in nociceptors, limiting the baseline sensitivity of these neurons. In this project, the role of the RNA-binding protein, Pumilio, in nociception was investigated using Drosophila melanogaster larvae as a model organism. RNAi knockdowns of pum lead to nociceptive hypersensitivity to mechanical, thermal, and chemical stimulus. When chronic pain was modeled with an injury-induced hypersensitivity assay, pumOE blocked sensitivity from increasing after injury.<p></p>