Small molecule kinase inhibitors alleviate different molecular features of myotonic dystrophy type 1

Marzena Wojciechowska, Katarzyna Taylor, Krzysztof Sobczak, Marek Napierala, Wlodzimierz J. Krzyzosiak

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Expandable (CTG)n repeats in the 3′ UTR of the DMPK gene are a cause of myotonic dystrophy type 1 (DM1), which leads to a toxic RNA gain-of-function disease. Mutant RNAs with expanded CUG repeats are retained in the nucleus and aggregate in discrete inclusions. These foci sequester splicing factors of the MBNL family and trigger upregulation of the CUGBP family of proteins resulting in the mis-splicing of their target transcripts. To date, many efforts to develop novel therapeutic strategies have been focused on disrupting the toxic nuclear foci and correcting aberrant alternative splicing via targeting mutant CUG repeats RNA; however, no effective treatment for DM1 is currently available. Herein, we present results of culturing of human DM1 myoblasts and fibroblasts with two small-molecule ATP-binding site-specific kinase inhibitors, C16 and C51, which resulted in the alleviation of the dominant-negative effects of CUG repeat expansion. Reversal of the DM1 molecular phenotype includes a reduction of the size and number of foci containing expanded CUG repeat transcripts, decreased steady-state levels of CUGBP1 protein, and consequent improvement of the aberrant alternative splicing of several pre-mRNAs misregulated in DM1.

Original languageEnglish (US)
JournalRNA Biology
Issue number6
StatePublished - Jun 2014
Externally publishedYes


  • CUG foci
  • CUGBP1 protein
  • MBNL1 protein
  • Myotonic dystrophy
  • Protein kinases
  • Protein phosphorylation
  • RNA splicing
  • RNA-binding proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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