Author/Editor | Savas, Jeffrey N; Makusky, Anthony; Ottosen, Soren; Baillat, David; Then, Florian; Krainc, Dimitri; Shiekhattar, Ramin; Markey, Sanford P; Tanese, Naoko | |
Title | Huntington's disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P bodies | |
Type | članek | |
Source | Proc Natl Acad Sci U S A | |
Vol. and No. | Letnik 105, št. 31 | |
Publication year | 2008 | |
Volume | str. 10820-5 | |
Language | eng | |
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. | |
Descriptors | FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT MICROSCOPY, CONFOCAL NERVE TISSUE PROTEINS NUCLEAR PROTEINS |