Abstract
Proper neurological function in humans requires precise control of levels of the epigenetic regulator methyl CpGbinding 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.
Original language | English |
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Pages (from-to) | 485-490 |
Number of pages | 6 |
Journal | Genes and Development |
Volume | 27 |
Issue number | 5 |
DOIs | |
Publication status | Published - 2013 Mar 1 |
Externally published | Yes |
Keywords
- 3' UTR
- HDAC4
- Human fetal brain
- MeCP2
- TBL1X
- miR-483-5p
ASJC Scopus subject areas
- Genetics
- Developmental Biology