First Author | Savas JN | Year | 2008 |
Journal | Proc Natl Acad Sci U S A | Volume | 105 |
Issue | 31 | Pages | 10820-5 |
PubMed ID | 18669659 | Mgi Jnum | J:140052 |
Mgi Id | MGI:3811682 | Doi | 10.1073/pnas.0800658105 |
Citation | Savas JN, et al. (2008) Huntington's disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P bodies. Proc Natl Acad Sci U S A 105(31):10820-5 |
abstractText | 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. |