RNA-dominant diseases

Hum Mol Genet. 2006 Oct 15;15 Spec No 2:R162-9. doi: 10.1093/hmg/ddl181.


Several examples have come to light in which mutations in non-protein-coding regions give rise to a deleterious gain-of-function by non-coding RNA. Expression of the toxic RNA is associated with formation of nuclear inclusions and late-onset degenerative changes in brain, heart or skeletal muscle. In the best studied example, myotonic dystrophy, it appears that the main pathogenic effect of the toxic RNA is to sequester binding proteins and compromise the regulation of alternative splicing. This review describes some of the recent advances in understanding the pathophysiology of RNA-dominant diseases.

Publication types

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

MeSH terms

  • Alternative Splicing
  • Fragile X Syndrome / genetics
  • Fragile X Syndrome / physiopathology
  • Genetic Diseases, Inborn / genetics*
  • Genetic Diseases, Inborn / physiopathology
  • Humans
  • Huntingtin Protein
  • Models, Genetic
  • Myotonic Dystrophy / genetics
  • Myotonic Dystrophy / physiopathology
  • Nerve Tissue Proteins / genetics
  • Nuclear Proteins / genetics
  • Phenotype
  • RNA, Untranslated / genetics*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Spinocerebellar Ataxias / genetics
  • Spinocerebellar Ataxias / physiopathology
  • Trinucleotide Repeat Expansion


  • HTT protein, human
  • Huntingtin Protein
  • MBNL1 protein, human
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • RNA, Untranslated
  • RNA-Binding Proteins