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 associat...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2008-08, Vol.105 (31), p.10820-10825 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Savas, Jeffrey N Makusky, Anthony Ottosen, Søren Baillat, David Then, Florian Krainc, Dimitri Shiekhattar, Ramin Markey, Sanford P Tanese, Naoko |
| description | 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. |
| doi_str_mv | 10.1073/pnas.0800658105 |
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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. 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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.</description><subject>Antibodies</subject><subject>Argonaute Proteins</subject><subject>Biological Sciences</subject><subject>Cells</subject><subject>Cytoplasmic Structures - metabolism</subject><subject>Eukaryotic Initiation Factor-2 - metabolism</subject><subject>Fluorescent Antibody Technique, Indirect</subject><subject>Genes</subject><subject>HeLa cells</subject><subject>Humans</subject><subject>Huntingtin Protein</subject><subject>Huntington disease</subject><subject>Huntingtons disease</subject><subject>Journalism</subject><subject>Messenger RNA</subject><subject>MicroRNA</subject><subject>MicroRNAs - metabolism</subject><subject>Microscopy, Confocal</subject><subject>Mutation</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Neurons</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Proteins</subject><subject>RNA</subject><subject>RNA Interference</subject><subject>Rodents</subject><subject>Small interfering RNA</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQhSMEokvhzAmwOIA4pB07dmJfkFYVUKQKENCz5SSTXa-y9mI7FP49jnbVBS49zWG-9zzPryieUjij0FTnO2fiGUiAWkgK4l6xoKBoWXMF94sFAGtKyRk_KR7FuAEAJSQ8LE6orGtVC7Uobi4nl6xbJe9eR9LbiCYi2QWf0DrSeZeCbaeEkSRPvn5allvsrUnYkxU6JNGO6LqsJ2kd_LRaExOj7zJhvSM3Nq3JMqy8M9mCGNeTL6T1vcX4uHgwmDHik8M8La7fv_t-cVleff7w8WJ5VXZC8FQOTdsYbFvEipscU3GhTC87LpqmQdYYYFRUkrWqrw2lapBN14BgsmemVi2rTou3e9_d1ObTO8yBzKh3wW5N-K29sfrfjbNrvfI_NRPAJYhs8OpgEPyPCWPSWxs7HEfj0E9R16pSkgPcCVKV_aRQGXz5H7jxU3D5FzQDWkmp1Ox2voe64GMMONyeTEHP1eu5en2sPiue_530yB-6zgA5ALPyaCd0RfOQbH71zR2IHqZxTPgrZfbZnt3E5MMtzASvK8bne17s94Px2qyCjfr62xwwt8gYr2j1B91611M</recordid><startdate>20080805</startdate><enddate>20080805</enddate><creator>Savas, Jeffrey N</creator><creator>Makusky, Anthony</creator><creator>Ottosen, Søren</creator><creator>Baillat, David</creator><creator>Then, Florian</creator><creator>Krainc, Dimitri</creator><creator>Shiekhattar, Ramin</creator><creator>Markey, Sanford P</creator><creator>Tanese, Naoko</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20080805</creationdate><title>Huntington's disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P bodies</title><author>Savas, Jeffrey N ; 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| subjects | Antibodies Argonaute Proteins Biological Sciences Cells Cytoplasmic Structures - metabolism Eukaryotic Initiation Factor-2 - metabolism Fluorescent Antibody Technique, Indirect Genes HeLa cells Humans Huntingtin Protein Huntington disease Huntingtons disease Journalism Messenger RNA MicroRNA MicroRNAs - metabolism Microscopy, Confocal Mutation Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Neurons Nuclear Proteins - genetics Nuclear Proteins - metabolism Proteins RNA RNA Interference Rodents Small interfering RNA |
| title | Huntington's disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P bodies |
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