Promoter-bound trinucleotide repeat mRNA drives epigenetic silencing in fragile X syndrome Academic Article uri icon


MeSH Major

  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome
  • Gene Silencing
  • RNA, Messenger
  • Trinucleotide Repeats


  • Epigenetic gene silencing is seen in several repeat-expansion diseases. In fragile X syndrome, the most common genetic form of mental retardation, a CGG trinucleotide-repeat expansion adjacent to the fragile X mental retardation 1 (FMR1) gene promoter results in its epigenetic silencing. Here, we show that FMR1 silencing is mediated by the FMR1 mRNA. The FMR1 mRNA contains the transcribed CGG-repeat tract as part of the 5' untranslated region, which hybridizes to the complementary CGG-repeat portion of the FMR1 gene to form an RNA┬ĚDNA duplex. Disrupting the interaction of the mRNA with the CGG-repeat portion of the FMR1 gene prevents promoter silencing. Thus, our data link trinucleotide-repeat expansion to a form of RNA-directed gene silencing mediated by direct interactions of the trinucleotide-repeat RNA and DNA.

publication date

  • January 2014



  • Academic Article



  • eng

PubMed Central ID

  • PMC4357282

Digital Object Identifier (DOI)

  • 10.1126/science.1245831

PubMed ID

  • 24578575

Additional Document Info

start page

  • 1002

end page

  • 5


  • 343


  • 6174