title: Altered splicing of Tau in DM1 is different from the foetal splicing process.
abstract: 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.
authors.affiliation: Inserm U837 - Jean-Pierre Aubert Research Centre, Université de Lille, Institut de Médecine Prédictive et Recherche Thérapeutique, Place de Verdun, F-59045 Lille Cedex, France.
authors.forename: Dana
authors.initials: D
authors.lastname: Ghanem
authors.forename: Hélène
authors.initials: H
authors.lastname: Tran
authors.forename: Claire-Marie
authors.initials: CM
authors.lastname: Dhaenens
authors.forename: Suzanna
authors.initials: S
authors.lastname: Schraen-Maschke
authors.forename: Bernard
authors.initials: B
authors.lastname: Sablonnière
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sergeant
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Caillet-Boudin
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D017398:Alternative Splicing; D045744:Cell Line, Tumor; D005091:Exons; D005333:Fetus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009223:Myotonic Dystrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010957:Plasmids; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D020033:Protein Isoforms; D016875:tau Proteins