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

Jeffrey N. Savas, Anthony Makusky, Søren Ottosen, David Baillat, Florian Then, Dimitri Krainc, Ramin Shiekhattar, Sanford P. Markey, Naoko Tanese

Research output: Contribution to journalArticle

111 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)10820-10825
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number31
StatePublished - Aug 5 2008
Externally publishedYes



  • Neuronal RNA granule
  • Poly-glutamine
  • Post-transcriptional gene silencing
  • RNA interference
  • microRNA

ASJC Scopus subject areas

  • General

Cite this