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

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  • 1Department of Microbiology and New York University Cancer Institute, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.


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.

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