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

Juan 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

281 Citations (Scopus)

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
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

Fingerprint

Methyl-CpG-Binding Protein 2
RNA Splicing
Methylation
Rett Syndrome
Y-Box-Binding Protein 1
X-Linked Mental Retardation
X-Linked Genes
Mutation
Motor Skills
RNA-Binding Proteins
Alternative Splicing
Autistic Disorder
Psychiatry
Language
RNA
Phenotype
Gene Expression

Keywords

  • Rett syndrome
  • Y box-binding protein 1

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2. / Young, Juan; Hong, Eugene P.; Castle, John C.; Crespo-Barreto, Juan; Bowman, Aaron B.; Rose, Matthew F.; Kang, Dongcheul; Richman, Ron; Johnson, Jason M.; Berget, Susan; Zoghbi, Huda Y.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 49, 06.12.2005, p. 17551-17558.

Research output: Contribution to journalArticle

Young, J, Hong, EP, Castle, JC, Crespo-Barreto, J, Bowman, AB, Rose, MF, Kang, D, Richman, R, Johnson, JM, Berget, S & Zoghbi, HY 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, vol. 102, no. 49, pp. 17551-17558. https://doi.org/10.1073/pnas.0507856102
Young, Juan ; Hong, Eugene P. ; Castle, John C. ; Crespo-Barreto, Juan ; Bowman, Aaron B. ; Rose, Matthew F. ; Kang, Dongcheul ; Richman, Ron ; Johnson, Jason M. ; Berget, Susan ; Zoghbi, Huda Y. / Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 49. pp. 17551-17558.
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