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Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p.
- Source :
-
Genes & Development . Mar2013, Vol. 27 Issue 5, p485-490. 6p. - Publication Year :
- 2013
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *FETAL brain
*MICRORNA
*EPIGENETICS
*CARRIER proteins
Subjects
Details
- Language :
- English
- ISSN :
- 08909369
- Volume :
- 27
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Genes & Development
- Publication Type :
- Academic Journal
- Accession number :
- 88008451
- Full Text :
- https://doi.org/10.1101/gad.207456.112