First Author | Han K | Year | 2013 |
Journal | Genes Dev | Volume | 27 |
Issue | 5 | Pages | 485-90 |
PubMed ID | 23431031 | Mgi Jnum | J:193960 |
Mgi Id | MGI:5469985 | Doi | 10.1101/gad.207456.112 |
Citation | Han K, et al. (2013) Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p. Genes Dev 27(5):485-90 |
abstractText | 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. |