Selective silencing of mutated mRNAs in DM1 by using modified hU7-snRNAs

Nat Struct Mol Biol. 2011 Jan;18(1):85-7. doi: 10.1038/nsmb.1958. Epub 2010 Dec 26.


We describe a function for modified human U7 small nuclear RNAs (hU7-snRNAs) distinct from modification of pre-mRNA splicing events. Engineered hU7-snRNAs containing a poly-CAG antisense sequence targeting the expanded CUG repeats of mutant DMPK transcripts in myotonic dystrophy caused specific degradation of pathogenic DMPK mRNAs without affecting the products of wild-type DMPK alleles. Abolition of the RNA gain-of-function toxicity that is responsible for pathogenesis supports the use of hU7-snRNAs for gene silencing in RNA-dominant disorders in which expanded repeats are expressed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Cells, Cultured
  • DNA Repeat Expansion
  • Gene Silencing*
  • Genetic Engineering
  • Humans
  • Myotonic Dystrophy / genetics
  • Myotonin-Protein Kinase
  • Protein-Serine-Threonine Kinases / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Nuclear / chemistry
  • RNA, Small Nuclear / metabolism
  • RNA, Small Nuclear / physiology*


  • DMPK protein, human
  • RNA, Messenger
  • RNA, Small Nuclear
  • U7 small nuclear RNA
  • Myotonin-Protein Kinase
  • Protein-Serine-Threonine Kinases