1. Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p
- Author
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Han, Kihoon, Gennarino, Vincenzo Alessandro, Lee, Yoontae, Pang, Kaifang, Hashimoto-Torii, Kazue, Choufani, Sanaa, Raju, Chandrasekhar S, Oldham, Michael C, Weksberg, Rosanna, Rakic, Pasko, Liu, Zhandong, and Zoghbi, Huda Y
- Subjects
Biological Sciences ,Biomedical and Clinical Sciences ,Psychology ,Rett Syndrome ,Neurodegenerative ,Rare Diseases ,Neurosciences ,Biotechnology ,Pediatric ,Genetics ,Brain Disorders ,Underpinning research ,1.1 Normal biological development and functioning ,Aetiology ,2.1 Biological and endogenous factors ,Binding Sites ,Brain ,Cell Line ,Fetus ,Gene Expression Regulation ,Developmental ,Genomic Imprinting ,Humans ,Methyl-CpG-Binding Protein 2 ,MicroRNAs ,Neurons ,Protein Binding ,MeCP2 ,human fetal brain ,UTR ,miR-483-5p ,HDAC4 ,TBL1X ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences - 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.
- Published
- 2013