Huntington's disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P bodies

Jeffrey N. Savas; Anthony Makusky; Søren Ottosen; David Baillat; Florian Then; Dimitri Krainc; Ramin Shiekhattar; Sanford P. Markey; Naoko Tanese

doi:10.1073/pnas.0800658105

Huntington's disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P bodies

Jeffrey N. Savas, Anthony Makusky, Søren Ottosen, David Baillat, Florian Then, Dimitri Krainc, Ramin Shiekhattar, Sanford P. Markey, Naoko Tanese

Research output: Contribution to journal › Article › peer-review

116 Scopus citations

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.

Original language	English (US)
Pages (from-to)	10820-10825
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	105
Issue number	31
DOIs	https://doi.org/10.1073/pnas.0800658105
State	Published - Aug 5 2008
Externally published	Yes

Keywords

Neuronal RNA granule
Poly-glutamine
Post-transcriptional gene silencing
RNA interference
microRNA

ASJC Scopus subject areas

General

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10.1073/pnas.0800658105

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Savas, J. N., Makusky, A., Ottosen, S., Baillat, D., Then, F., Krainc, D., Shiekhattar, R., Markey, S. P., & Tanese, N. (2008). Huntington's disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P bodies. Proceedings of the National Academy of Sciences of the United States of America, 105(31), 10820-10825. https://doi.org/10.1073/pnas.0800658105

Huntington's disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P bodies. / Savas, Jeffrey N.; Makusky, Anthony; Ottosen, Søren et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 31, 05.08.2008, p. 10820-10825.

Research output: Contribution to journal › Article › peer-review

Savas, JN, Makusky, A, Ottosen, S, Baillat, D, Then, F, Krainc, D, Shiekhattar, R, Markey, SP & Tanese, N 2008, 'Huntington's disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P bodies', Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 31, pp. 10820-10825. https://doi.org/10.1073/pnas.0800658105

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AU - Then, Florian

AU - Krainc, Dimitri

AU - Shiekhattar, Ramin

AU - Markey, Sanford P.

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Huntington's disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P bodies

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