Brain-specific change in alternative splicing of Tau exon 6 in myotonic dystrophy type 1
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Authors
Leroy, OlivierWang, Junning
Maurage, Claude-Alain
Parent, Michel
Cooper, Thomas
Buee, Luc
Sergeant, Nicolas
Andreadis, Athena
Caillet-Boudin, Marie-Laure
UMass Chan Affiliations
Department of Cell Biology,Shriver CenterDocument Type
Journal ArticlePublication Date
2006-02-21Keywords
*Alternative SplicingBrain
CCAAT-Enhancer-Binding Protein-delta
Cell Line
*Exons
Humans
Middle Aged
Muscle, Skeletal
Myotonic Dystrophy
Nerve Tissue Proteins
Neuroglia
Neurons
Protein-Serine-Threonine Kinases
RNA-Binding Proteins
tau Proteins
Cell Biology
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Show full item recordAbstract
Alternative splicing is altered in myotonic dystrophy of type 1 (DM1), a syndrome caused by an increase of CTG triplet repeats in the 3' untranslated region of the myotonic dystrophy protein kinase gene. Previously, we reported the preferential skipping of Tau exon 2 in DM1 brains. In this study, we analyze the alternative splicing of Tau exon 6 which can be inserted in three different forms (c, p and d) depending on the 3' splice site used. In fact, inclusion of exon 6c decreases in DM1 brains compared to control brains whereas inclusion of 6d increases. Alteration of exon 6 splicing was not observed in DM1 muscle although this exon was inserted in RNAs from normal muscle and DM1 splicing alterations were first described in this organ. In contrast, alteration of exon 2 of Tau mRNA was observed in both muscle and brain. However, co-transfections of a minigene containing exon 6 with CELF or MBNL1 cDNAs, two splicing factor families suspected to be involved in DM1, showed that they influence exon 6 splicing. Altogether, these results show the importance of determining all the exons and organs targeted by mis-splicing to determine the dysregulation mechanisms of mis-splicing in DM1.Source
Biochim Biophys Acta. 2006 Apr;1762(4):460-7. Epub 2005 Dec 29. Link to article on publisher's siteDOI
10.1016/j.bbadis.2005.12.003Permanent Link to this Item
http://hdl.handle.net/20.500.14038/25692PubMed ID
16487687Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.bbadis.2005.12.003
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