Design of a "Mini" Nucleic Acid Probe for Cooperative Binding of an RNA-Repeated Transcript Associated with Myotonic Dystrophy Type 1

Biochemistry. 2018 Feb 13;57(6):907-911. doi: 10.1021/acs.biochem.7b01239. Epub 2018 Jan 19.


Toxic RNAs containing expanded trinucleotide repeats are the cause of many neuromuscular disorders, one being myotonic dystrophy type 1 (DM1). DM1 is triggered by CTG-repeat expansion in the 3'-untranslated region of the DMPK gene, resulting in a toxic gain of RNA function through sequestration of MBNL1 protein, among others. Herein, we report the development of a relatively short miniPEG-γ peptide nucleic acid probe, two triplet repeats in length, containing terminal pyrene moieties, that is capable of binding rCUG repeats in a sequence-specific and selective manner. The newly designed probe can discriminate the pathogenic rCUGexp from the wild-type transcript and disrupt the rCUGexp-MBNL1 complex. The work provides a proof of concept for the development of relatively short nucleic acid probes for targeting RNA-repeat expansions associated with DM1 and other related neuromuscular disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Base Sequence
  • Binding Sites
  • Humans
  • Myotonic Dystrophy / genetics
  • Myotonic Dystrophy / metabolism*
  • Myotonin-Protein Kinase / genetics
  • Myotonin-Protein Kinase / metabolism
  • Peptide Nucleic Acids / chemistry
  • Peptide Nucleic Acids / genetics
  • Peptide Nucleic Acids / metabolism*
  • RNA / chemistry
  • RNA / genetics
  • RNA / metabolism*
  • RNA Probes / chemistry
  • RNA Probes / genetics
  • RNA Probes / metabolism*
  • RNA-Binding Proteins / metabolism
  • Trinucleotide Repeat Expansion*


  • DMPK protein, human
  • MBNL1 protein, human
  • Peptide Nucleic Acids
  • RNA Probes
  • RNA-Binding Proteins
  • RNA
  • Myotonin-Protein Kinase