title: Reciprocal regulation of autism-related genes MeCP2 and PTEN via microRNAs.
abstract: MeCP2 encodes a methyl-CpG-binding protein that plays a critical role in repressing gene expression, mutations of which lead to Rett syndrome and autism. PTEN is a critical tumor suppressor gene that is frequently mutated in human cancers and autism spectrum disorders. Various studies have shown that both MeCP2 and PTEN proteins play important roles in brain development. Here we find that MeCP2 and PTEN reciprocally regulate expression of each other via microRNAs. Knockdown of MeCP2 leads to upregulation of microRNA-137, which in turn represses expression of PTEN, thus PTEN would be down-regulated when MeCP2 is knockdown. Furthermore, we find that deletion of PTEN leads to phosphorylation of Serine 133 of CREB, then increases the expression of microRNA-132. miR-132 inhibits the expression of MeCP2 by targeting on the 3'UTR of MeCP2 mRNA. Our work shows that two critical disorders-related gene MeCP2 and PTEN reciprocally regulate expression of each other by distinct mechanisms, suggesting that rare mutations in various disorders may lead to dysregulation of other critical genes and yield unexpected consequences.
authors: Departments of Neonatology, Children's Hospital of Fudan University, Shanghai 201102, China.
authors: Jing-Wen
authors: JW
authors: Lyu
authors: Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Bo
authors: B
authors: Yuan
authors: Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Tian-Lin
authors: TL
authors: Cheng
authors: Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Zi-Long
authors: ZL
authors: Qiu
authors: Departments of Neonatology, Children's Hospital of Fudan University, Shanghai 201102, China.|Key Laboratory of Birth Defects, Children's Hospital, Fudan University, Shanghai 201102, China.
authors: Wen-Hao
authors: WH
authors: Zhou
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001321:Autistic Disorder / Q000235:genetics / Q000473:pathology; D015153:Blotting, Western; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017423:Sequence Analysis, RNA; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D017362:Cyclic AMP Response Element-Binding Protein; D051783:Methyl-CpG-Binding Protein 2; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051059:PTEN Phosphohydrolase