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

Juan I. Young, Eugene P. Hong, John C. Castle, Juan Crespo-Barreto, Aaron B. Bowman, Matthew F. Rose, Dongcheul Kang, Ron Richman, Jason M. Johnson, Susan Berget, Huda Y. Zoghbi

Research output: Contribution to journalArticle

300 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)17551-17558
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number49
DOIs
StatePublished - Dec 6 2005
Externally publishedYes

Keywords

  • Rett syndrome
  • Y box-binding protein 1

ASJC Scopus subject areas

  • Genetics
  • General

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    Young, J. I., Hong, E. P., Castle, J. C., Crespo-Barreto, J., Bowman, A. B., Rose, M. F., Kang, D., Richman, R., Johnson, J. M., Berget, S., & Zoghbi, H. Y. (2005). Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2. Proceedings of the National Academy of Sciences of the United States of America, 102(49), 17551-17558. https://doi.org/10.1073/pnas.0507856102