title: MiR-130a regulates neurite outgrowth and dendritic spine density by targeting MeCP2.
abstract: MicroRNAs (miRNAs) are critical for both development and function of the central nervous system. Significant evidence suggests that abnormal expression of miRNAs is associated with neurodevelopmental disorders. MeCP2 protein is an epigenetic regulator repressing or activating gene transcription by binding to methylated DNA. Both loss-of-function and gain-of-function mutations in the MECP2 gene lead to neurodevelopmental disorders such as Rett syndrome, autism and MECP2 duplication syndrome. In this study, we demonstrate that miR-130a inhibits neurite outgrowth and reduces dendritic spine density as well as dendritic complexity. Bioinformatics analyses, cell cultures and biochemical experiments indicate that miR-130a targets MECP2 and down-regulates MeCP2 protein expression. Furthermore, expression of the wild-type MeCP2, but not a loss-of-function mutant, rescues the miR-130a-induced phenotype. Our study uncovers the MECP2 gene as a previous unknown target for miR-130a, supporting that miR-130a may play a role in neurodevelopment by regulating MeCP2. Together with data from other groups, our work suggests that a feedback regulatory mechanism involving both miR-130a and MeCP2 may serve to ensure their appropriate expression and function in neural development.
authors.affiliation: State Key Laboratory for Brain & Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Yunjia
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory for Brain & Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Chen
authors.affiliation: Laboratory of Molecular Basis of Neural Plasticity, Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Zilong
authors.initials: Z
authors.lastname: Qiu
authors.affiliation: Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences, Beijing, 100193, China.
authors.forename: Keping
authors.initials: K
authors.lastname: Hu
authors.affiliation: Department of Neurology, Center for Genetic Medicine, Lurie Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
authors.forename: Warren
authors.initials: W
authors.lastname: McGee
authors.affiliation: Department of Neurology, Center for Genetic Medicine, Lurie Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory for Brain & Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Jianghong
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory for Brain & Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. zhuli@moon.ibp.ac.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.affiliation: State Key Laboratory for Brain & Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. jane-wu@northwestern.edu.|Department of Neurology, Center for Genetic Medicine, Lurie Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA. jane-wu@northwestern.edu.
authors.forename: Jane Y
authors.initials: JY
authors.lastname: Wu
mesh_terms: D000818:Animals; D003712:Dendrites / Q000235:genetics / Q000378:metabolism*; D049229:Dendritic Spines / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology*; D051783:Methyl-CpG-Binding Protein 2 / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051381:Rats
chemical_list: C569198:MIRN130 microRNA, rat; C497394:Mecp2 protein, rat; D051783:Methyl-CpG-Binding Protein 2; D035683:MicroRNAs
keywords: MECP2; dendrite morphology; dendritic spines; miR-130a; neurite outgrowth