Huntington's disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P bodies.
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.
Savas
Jeffrey N
JN
Department of Microbiology and New York University Cancer Institute, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
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
D060565:Argonaute Proteins; D022083:Cytoplasmic Structures / Q000378:metabolism*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D000071058:Huntingtin Protein; D035683:MicroRNAs / Q000378:metabolism*; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference
C466422:AGO2 protein, human; D060565:Argonaute Proteins; D015852:Eukaryotic Initiation Factor-2; C086055:HTT protein, human; D000071058:Huntingtin Protein; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins