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

106 Citations (Scopus)

Abstract

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
Volume105
Issue number31
DOIs
StatePublished - Aug 5 2008
Externally publishedYes

Fingerprint

Gene Silencing
RNA
Corpus Striatum
Huntington Disease
Reporter Genes
Neurodegenerative Diseases
Epitopes
Proteins
Huntingtin Protein
polyglutamine

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Huntington's disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P bodies. / Savas, Jeffrey N.; Makusky, Anthony; Ottosen, Søren; Baillat, David; Then, Florian; Krainc, Dimitri; Shiekhattar, Ramin; Markey, Sanford P.; Tanese, Naoko.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 31, 05.08.2008, p. 10820-10825.

Research output: Contribution to journalArticle

Savas, Jeffrey N. ; Makusky, Anthony ; Ottosen, Søren ; Baillat, David ; Then, Florian ; Krainc, Dimitri ; Shiekhattar, Ramin ; Markey, Sanford P. ; Tanese, Naoko. / Huntington's disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P bodies. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 31. pp. 10820-10825.
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