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

FEBS Lett. 2009 Feb 18;583(4):675-9. doi: 10.1016/j.febslet.2008.12.065. Epub 2009 Jan 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Alternative Splicing*
  • Cell Line, Tumor
  • Exons
  • Fetus / metabolism*
  • Fetus / pathology
  • Humans
  • Myotonic Dystrophy* / genetics
  • Myotonic Dystrophy* / metabolism
  • Myotonic Dystrophy* / pathology
  • Plasmids
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Transfection
  • tau Proteins / genetics
  • tau Proteins / metabolism*

Substances

  • 3' Untranslated Regions
  • Protein Isoforms
  • tau Proteins