期刊
GENES & DEVELOPMENT
卷 27, 期 5, 页码 485-490出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.207456.112
关键词
MeCP2; human fetal brain; 39 UTR; miR-483-5p; HDAC4; TBL1X
资金
- Howard Hughes Medical Institute
- NIH [5R01NS057819, R01-DA023999, R01-NS038296, NIH/NIAAA K99AA018387]
- Baylor Intellectual and Developmental Disabilities Research Center [P30HD024064]
- Wenner-Gren Foundations, Sweden
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.
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