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

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.

SUBMITTER: Savas JN

PROVIDER: S-EPMC2504805 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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

Savas Jeffrey N JN Makusky Anthony A Ottosen Søren S Baillat David D Then Florian F Krainc Dimitri D Shiekhattar Ramin R Markey Sanford P SP Tanese Naoko N

Proceedings of the National Academy of Sciences of the United States of America 20080731 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 show ...[more]

PMID: 18669659

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