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.

Abbreviations: DM, myotonic dystrophy, DMPK, dystrophia myotonia protein kinase, cTNT, cardiac troponin T, ClC-1, chloride channel-1, IR, insulin receptor

Keywords: Microtubule-associated protein Tau, Alternative splicing, Myotonic dystrophy, Development, Brain