Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p
SCIE
SCOPUS
- Title
- Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p
- Authors
- Han, K; Gennarino, VA; Lee, Y; Pang, KF; Hashimoto-Torii, K; Choufani, S; Raju, CS; Oldham, MC; Weksberg, R; Rakic, P; Liu, ZD; Zoghbi, HY
- Date Issued
- 2013-03-01
- Publisher
- Cold Spring Harbor Laboratory Press
- 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 39 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 39 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.
- Keywords
- MeCP2; human fetal brain; 39 UTR; miR-483-5p; HDAC4; TBL1X; CPG-BINDING PROTEIN-2; RETT-SYNDROME; ALTERNATIVE POLYADENYLATION; EXPRESSION; TRANSCRIPTION; DUPLICATION; COMPLEX; SYMPTOMS; AUTISM; REGION
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/13658
- DOI
- 10.1101/GAD.207456.112
- ISSN
- 0890-9369
- Article Type
- Article
- Citation
- GENES & DEVELOPMENT, vol. 27, no. 5, page. 485 - 490, 2013-03-01
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