RNA Control in Sensory Neurons: a Functional Genomics Approach

This work investigates the molecular mechanisms of pain signaling at the level of translation in sensory neurons. Pain-sensing neurons, or nociceptors, are integral to the genesis of many forms of chronic pain. Here, we apply functional genomics approaches to examine the role of translational control in pain. High-throughput sequencing experiments reveal potential molecular targets, which are confirmed using pharmacology, electrophysiology, and behavioral methods. With these methods, we examine the role of the nonsense mediated decay (NMD) pathway, eukaryotic initiation factor 5A (eIF5A), and the S6 ribosomal protein kinase 1 (S6K1) in pain. Along with these findings, we investigate the use of human induced pluripotent stem cell (hiPSC)-derived sensory neurons in pain research using high-throughput RNA sequencing. We also present one of the few datasets employing ribosome profiling on the dorsal root ganglion (DRG) in the presence of inflammatory mediators. Lastly, we show our foundational work linking NMD to pain. Overall, these findings highlight the role of translational control in pain.