MicroRNA Regulation of nAChR Expression and Nicotine-Dependent Behavior in C. elegans
Manish Rauthan,
Jianke Gong,
Jinzhi Liu,
Zhaoyu Li,
Seth A. Wescott,
Jianfeng Liu,
X.Z. Shawn Xu
Affiliations
Manish Rauthan
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
Jianke Gong
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; College of Life Science and Technology, Key Laboratory of Molecular Biophysics of MOE, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China
Jinzhi Liu
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; College of Life Science and Technology, Key Laboratory of Molecular Biophysics of MOE, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China
Zhaoyu Li
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
Seth A. Wescott
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA
Jianfeng Liu
College of Life Science and Technology, Key Laboratory of Molecular Biophysics of MOE, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China
X.Z. Shawn Xu
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA; Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA; Corresponding author
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
