Huntington's disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P bodies

Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10820-5. doi: 10.1073/pnas.0800658105. Epub 2008 Jul 31.


Huntington's disease is a dominant autosomal neurodegenerative disorder caused by an expansion of polyglutamines in the huntingtin (Htt) protein, whose cellular function remains controversial. To gain insight into Htt function, we purified epitope-tagged Htt and identified Argonaute as associated proteins. Colocalization studies demonstrated Htt and Ago2 to be present in P bodies, and depletion of Htt showed compromised RNA-mediated gene silencing. Mouse striatal cells expressing mutant Htt showed fewer P bodies and reduced reporter gene silencing activity compared with wild-type counterparts. These data suggest that the previously reported transcriptional deregulation in HD may be attributed in part to mutant Htt's role in post-transcriptional processes.

Publication types

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

MeSH terms

  • Argonaute Proteins
  • Cytoplasmic Structures / metabolism*
  • Eukaryotic Initiation Factor-2 / metabolism*
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Huntingtin Protein
  • MicroRNAs / metabolism*
  • Microscopy, Confocal
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA Interference*


  • AGO2 protein, human
  • Argonaute Proteins
  • Eukaryotic Initiation Factor-2
  • HTT protein, human
  • Huntingtin Protein
  • MicroRNAs
  • Nerve Tissue Proteins
  • Nuclear Proteins