Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p

Genes Dev. 2013 Mar 1;27(5):485-90. doi: 10.1101/gad.207456.112. Epub 2013 Feb 21.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Brain / embryology
  • Brain / metabolism*
  • Brain / physiopathology
  • Cell Line
  • Fetus / embryology
  • Fetus / metabolism
  • Fetus / physiopathology
  • Gene Expression Regulation, Developmental*
  • Genomic Imprinting
  • Humans
  • Methyl-CpG-Binding Protein 2 / genetics*
  • Methyl-CpG-Binding Protein 2 / metabolism*
  • MicroRNAs / metabolism*
  • Neurons / metabolism*
  • Neurons / pathology
  • Protein Binding


  • MIRN483 microRNA, human
  • Methyl-CpG-Binding Protein 2
  • MicroRNAs