The RNA-binding protein Pumilio limits polymodal nociception in Drosophila larvae

Nociception is the process by which the nervous system detects and processes information about potentially harmful environmental stimuli to generate behavioral and physiological responses. The process of nociception undergoes plasticity in response to injury, inflammation, and infection to shape the sensitivity of nociceptive circuits and the behavioral responses they control. We are increasingly aware that post-transcriptional regulation of gene expression shapes the sensitivity and plasticity of nociceptive sensory neurons and nociceptive behavior. In Drosophila, the Pumilio RNA-binding protein interacts with diverse target mRNAs to regulate their abundance and translation in a wide range of contexts including the establishment of embryonic polarity, maintenance of the germline, regulation of neural morphology, and homeostatic control of neural excitability. In this study, we find that Pumilio acts to limit nociceptive sensitivity through its activity in nociceptive sensory neurons. Larvae with nociceptor-specific pumilio knockdown show enhanced nocifensive responses to noxious thermal, mechanical, and chemical stimuli, while larvae with nociceptor-specific overexpression of pumilio show blunted responses to noxious thermal and mechanical sensitivity. Furthermore, we find that Pumilio is required in the nociceptors for larvae to expression nociceptive sensitization following injury, suggesting a role for Pumilio in nociceptor plasticity. These observations may be explained by regulation of neuronal excitability, dendrite morphology, and cell signaling by Pumilio, and future studies will elucidate these mechanisms.