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Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2.

Rett syndrome (RTT) is a postnatal neurodevelopmental disorder characterized by the loss of acquired motor and language skills, autistic features, and unusual stereotyped movements. RTT is caused by mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2). Mutations in MECP2 cause a variety of neurodevelopmental disorders including X-linked mental retardation, psychiatric disorders, and some cases of autism. Although MeCP2 was identified as a methylation-dependent transcriptional repressor, transcriptional profiling of RNAs from mice lacking MeCP2 did not reveal significant gene expression changes, suggesting that MeCP2 does not simply function as a global repressor. Changes in expression of a few genes have been observed, but these alterations do not explain the full spectrum of Rett-like phenotypes, raising the possibility that additional MeCP2 functions play a role in pathogenesis. In this study, we show that MeCP2 interacts with the RNA-binding protein Y box-binding protein 1 and regulates splicing of reporter minigenes. Importantly, we found aberrant alternative splicing patterns in a mouse model of RTT. Thus, we uncovered a previously uncharacterized function of MeCP2 that involves regulation of splicing, in addition to its role as a transcriptional repressor.

Pubmed ID: 16251272


  • Young JI
  • Hong EP
  • Castle JC
  • Crespo-Barreto J
  • Bowman AB
  • Rose MF
  • Kang D
  • Richman R
  • Johnson JM
  • Berget S
  • Zoghbi HY


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

December 6, 2005

Associated Grants

  • Agency: NICHD NIH HHS, Id: HD24064

Mesh Terms

  • Animals
  • Cell Line, Tumor
  • DNA Methylation
  • Exons
  • Gene Expression Profiling
  • Genes, Reporter
  • Humans
  • Methyl-CpG-Binding Protein 2
  • Mice
  • Models, Genetic
  • Protein Binding
  • RNA
  • RNA Splicing
  • Rett Syndrome
  • Transcription, Genetic