MicroRNA Regulation of nAChR Expression and Nicotine-Dependent Behavior in C. elegans

Abstract

Summary: Chronic exposure to nicotine upregulates nicotinic acetylcholine receptors (nAChRs), and such upregulation is critical for the development of nicotine dependence in humans and animal models. However, how nicotine upregulates nAChRs is not well understood. Here, we identify a key role for microRNA in regulating nicotine-dependent behavior by modulating nAChR expression in C. elegans. We show that the nAChR gene acr-19 and alg-1, a key Argonaute-family member in the microRNA machinery, are specifically required for nicotine withdrawal response following chronic nicotine treatment. Chronic exposure to nicotine downregulates alg-1, leading to upregulation of acr-19. This effect is mediated by the microRNA miR-238 that recognizes the 3′ UTR of acr-19 transcript. Our results unveil a previously unrecognized role for microRNA in nicotine signaling, providing insights into how chronic nicotine administration leads to upregulation of nAChR and ultimately nicotine dependence. : Chronic exposure to nicotine upregulates nAChR, which is critical for the development of nicotine dependence. However, the underlying mechanisms are not well understood. Here, the authors identify a key role for microRNA in mediating nicotine-induced upregulation of nAChR and nicotine-dependent behavior using a C. elegans model. Keywords: neuron, tobacco, addiction