Altered splicing of Tau in DM1 is different from the foetal splicing process

• Published in: FEBS letters 2009-02, Vol.583 (4), p.675-679
• Main Authors: Ghanem, Dana, Tran, Hélène, Dhaenens, Claire-Marie, Schraen-Maschke, Suzanna, Sablonnière, Bernard, Buée, Luc, Sergeant, Nicolas, Caillet-Boudin, Marie-Laure
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; Adult; Alternative Splicing; Brain; cardiac troponin T; Cell Line, Tumor; chloride channel-1; ClC-1; cTNT; Development; DMPK; dystrophia myotonia protein kinase; Exons; Fetus - metabolism; Fetus - pathology; Humans; insulin receptor; Microtubule-associated protein Tau; Myotonic dystrophy; Myotonic Dystrophy - genetics; Myotonic Dystrophy - metabolism; Myotonic Dystrophy - pathology; Plasmids; Protein Isoforms - genetics; Protein Isoforms - metabolism; tau Proteins - genetics; tau Proteins - metabolism; Transfection
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2008.12.065

Among the different mechanisms underlying the etiopathogenesis of myotonic dystrophy type 1 (DM1), a backward reprogramming to a foetal splicing machinery is an interesting hypothesis. To address this possibility, Tau splicing, which is regulated during development and modified in DM1, was analyzed. Indeed, a preferential expression of the foetal Tau isoform, instead of the six normally found, is observed in adult DM1 brains. By using two cell lines, we show here that the cis-regulating elements necessary to generate the unique foetal Tau isoform are dispensable to reproduce the trans-dominant effect induced by DM1 mutation on Tau exon 2 inclusion. Our results suggest that the mis-splicing of Tau in DM1 is resulting from a disease-associated mechanism.