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