In:
Genes & Development, Cold Spring Harbor Laboratory, Vol. 27, No. 5 ( 2013-03-01), p. 485-490
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.
Type of Medium:
Online Resource
ISSN:
0890-9369
,
1549-5477
DOI:
10.1101/gad.207456.112
Language:
English
Publisher:
Cold Spring Harbor Laboratory
Publication Date:
2013
detail.hit.zdb_id:
1467414-2
SSG:
12
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