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

  • Author(s): Han, K
  • Gennarino, VA
  • Lee, Y
  • Pang, K
  • Hashimoto-Torii, K
  • Choufani, S
  • Raju, CS
  • Oldham, MC
  • Weksberg, R
  • Rakic, P
  • Liu, Z
  • Zoghbi, HY
  • et al.
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. © 2013 by Cold Spring Harbor Laboratory Press.

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