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

Kihoon Han, Vincenzo Alessandro Gennarino, Yoontae Lee, Kaifang Pang, Kazue Hashimoto-Torii, Sanaa Choufani, Chandrasekhar S. Raju, Michael C. Oldham, Rosanna Weksberg, Pasko Rakic, Zhandong Liu, Huda Y. Zoghbi

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)485-490
Number of pages6
JournalGenes and Development
Volume27
Issue number5
DOIs
Publication statusPublished - 2013 Mar 1

Keywords

  • 3' UTR
  • HDAC4
  • Human fetal brain
  • MeCP2
  • TBL1X
  • miR-483-5p

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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