title: Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p.
abstract: Proper neurological function in humans requires precise control of levels of the epigenetic regulator methyl CpG-binding protein 2 (MeCP2). MeCP2 protein levels are low in fetal brains, where the predominant MECP2 transcripts have an unusually long 3' untranslated region (UTR). Here, we show that miR-483-5p, an intragenic microRNA of the imprinted IGF2, regulates MeCP2 levels through a human-specific binding site in the MECP2 long 3' UTR. We demonstrate the inverse correlation of miR-483-5p and MeCP2 levels in developing human brains and fibroblasts from Beckwith-Wiedemann syndrome patients. Importantly, expression of miR-483-5p rescues abnormal dendritic spine phenotype of neurons overexpressing human MeCP2. In addition, miR-483-5p modulates the levels of proteins of the MeCP2-interacting corepressor complexes, including HDAC4 and TBL1X. These data provide insight into the role of miR-483-5p in regulating the levels of MeCP2 and interacting proteins during human fetal development.
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors: Kihoon
authors: K
authors: Han
authors: Vincenzo Alessandro
authors: VA
authors: Gennarino
authors: Yoontae
authors: Y
authors: Lee
authors: Kaifang
authors: K
authors: Pang
authors: Kazue
authors: K
authors: Hashimoto-Torii
authors: Sanaa
authors: S
authors: Choufani
authors: Chandrasekhar S
authors: CS
authors: Raju
authors: Michael C
authors: MC
authors: Oldham
authors: Rosanna
authors: R
authors: Weksberg
authors: Pasko
authors: P
authors: Rakic
authors: Zhandong
authors: Z
authors: Liu
authors: Huda Y
authors: HY
authors: Zoghbi
mesh_terms: D001665:Binding Sites; D001921:Brain / Q000196:embryology / Q000378:metabolism* / Q000503:physiopathology; D002460:Cell Line; D005333:Fetus / Q000196:embryology / Q000378:metabolism / Q000503:physiopathology; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding
chemical_list: C548912:MIRN483 microRNA, human; D051783:Methyl-CpG-Binding Protein 2; D035683:MicroRNAs