Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2
| العنوان: | Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2 |
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| المؤلفون: | Eugene P. Hong, Juan Crespo-Barreto, Jason M. Johnson, Huda Y. Zoghbi, Aaron B. Bowman, Juan I. Young, John C. Castle, Susan M. Berget, Ron Richman, Matthew F. Rose, Dongcheul Kang |
| المصدر: | Proceedings of the National Academy of Sciences. 102:17551-17558 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | congenital, hereditary, and neonatal diseases and abnormalities, Transcription, Genetic, Methyl-CpG-Binding Protein 2, RNA Splicing, Repressor, Biology, MECP2, Mice, Exon, Genes, Reporter, Cell Line, Tumor, mental disorders, Rett Syndrome, Animals, Humans, Genetics, Multidisciplinary, Models, Genetic, YY1, Gene Expression Profiling, Alternative splicing, Exons, DNA Methylation, Biological Sciences, Y box binding protein 1, nervous system diseases, GATAD2B, RNA splicing, RNA, Protein Binding |
| الوصف: | 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. |
| تدمد: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0507856102 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7f6ce0ecf38e9fb9c5adb85f65819a03 https://doi.org/10.1073/pnas.0507856102 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7f6ce0ecf38e9fb9c5adb85f65819a03 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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| DOI: | 10.1073/pnas.0507856102 |