Human accelerated region 1 noncoding RNA is repressed by REST in Huntington's disease
In the neurons of Huntington's disease (HD) patients, gene regulatory networks are disrupted by aberrant nuclear localization of the master transcriptional repressor REST. Emerging evidence suggests that, in addition to protein-coding genes, noncoding RNAs (ncRNAs) may also contribute to neurod...
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| Veröffentlicht in: | Physiological genomics 2010-05, Vol.41 (3), p.269-274 |
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| container_title | Physiological genomics |
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| creator | Johnson, Rory Richter, Nadine Jauch, Ralf Gaughwin, Philip M Zuccato, Chiara Cattaneo, Elena Stanton, Lawrence W |
| description | In the neurons of Huntington's disease (HD) patients, gene regulatory networks are disrupted by aberrant nuclear localization of the master transcriptional repressor REST. Emerging evidence suggests that, in addition to protein-coding genes, noncoding RNAs (ncRNAs) may also contribute to neurodegenerative processes. To discover ncRNAs that are involved in HD, we screened genome-wide data for novel, noncoding targets of REST. This identified human accelerated region 1 (HAR1), a rapidly evolving cis-antisense locus that is specifically transcribed in the nervous system. We show that REST is targeted to the HAR1 locus by specific DNA regulatory motifs, resulting in potent transcriptional repression. Consistent with other REST target genes, HAR1 levels are significantly lower in the striatum of HD patients compared with unaffected individuals. These data represent further evidence that noncoding gene expression changes accompany neurodegeneration in Huntington's disease. |
| doi_str_mv | 10.1152/physiolgenomics.00019.2010 |
| format | Article |
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Emerging evidence suggests that, in addition to protein-coding genes, noncoding RNAs (ncRNAs) may also contribute to neurodegenerative processes. To discover ncRNAs that are involved in HD, we screened genome-wide data for novel, noncoding targets of REST. This identified human accelerated region 1 (HAR1), a rapidly evolving cis-antisense locus that is specifically transcribed in the nervous system. We show that REST is targeted to the HAR1 locus by specific DNA regulatory motifs, resulting in potent transcriptional repression. Consistent with other REST target genes, HAR1 levels are significantly lower in the striatum of HD patients compared with unaffected individuals. These data represent further evidence that noncoding gene expression changes accompany neurodegeneration in Huntington's disease.</description><identifier>ISSN: 1094-8341</identifier><identifier>EISSN: 1531-2267</identifier><identifier>DOI: 10.1152/physiolgenomics.00019.2010</identifier><identifier>PMID: 20179156</identifier><language>eng</language><publisher>United States</publisher><subject>3T3 Cells ; Animals ; Base Sequence ; HEK293 Cells ; HeLa Cells ; Humans ; Huntington Disease - genetics ; Mice ; Molecular Sequence Data ; Repressor Proteins - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; RNA, Untranslated - genetics ; RNA, Untranslated - metabolism</subject><ispartof>Physiological genomics, 2010-05, Vol.41 (3), p.269-274</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-6803252a2f5dac66a1cc34588b7dbab782e7bbfb79c79dff9b6b6444a096ebf33</citedby><cites>FETCH-LOGICAL-c442t-6803252a2f5dac66a1cc34588b7dbab782e7bbfb79c79dff9b6b6444a096ebf33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3026,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20179156$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Johnson, Rory</creatorcontrib><creatorcontrib>Richter, Nadine</creatorcontrib><creatorcontrib>Jauch, Ralf</creatorcontrib><creatorcontrib>Gaughwin, Philip M</creatorcontrib><creatorcontrib>Zuccato, Chiara</creatorcontrib><creatorcontrib>Cattaneo, Elena</creatorcontrib><creatorcontrib>Stanton, Lawrence W</creatorcontrib><title>Human accelerated region 1 noncoding RNA is repressed by REST in Huntington's disease</title><title>Physiological genomics</title><addtitle>Physiol Genomics</addtitle><description>In the neurons of Huntington's disease (HD) patients, gene regulatory networks are disrupted by aberrant nuclear localization of the master transcriptional repressor REST. Emerging evidence suggests that, in addition to protein-coding genes, noncoding RNAs (ncRNAs) may also contribute to neurodegenerative processes. To discover ncRNAs that are involved in HD, we screened genome-wide data for novel, noncoding targets of REST. This identified human accelerated region 1 (HAR1), a rapidly evolving cis-antisense locus that is specifically transcribed in the nervous system. We show that REST is targeted to the HAR1 locus by specific DNA regulatory motifs, resulting in potent transcriptional repression. Consistent with other REST target genes, HAR1 levels are significantly lower in the striatum of HD patients compared with unaffected individuals. These data represent further evidence that noncoding gene expression changes accompany neurodegeneration in Huntington's disease.</description><subject>3T3 Cells</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>HEK293 Cells</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Huntington Disease - genetics</subject><subject>Mice</subject><subject>Molecular Sequence Data</subject><subject>Repressor Proteins - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA, Untranslated - genetics</subject><subject>RNA, Untranslated - metabolism</subject><issn>1094-8341</issn><issn>1531-2267</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkD1PwzAQhi0EoqXwF5DFAkuK7fgjYUNVoUgVSKWdI9txilFihzgZ-u9xaWFgupPuee90DwA3GE0xZuS-_dgF6-utcb6xOkwRQjifEoTRCRhjluKEEC5OY49ymmQpxSNwEcJnxKjI2DkYRVbkmPEx2CyGRjootTa16WRvStiZrfUOYui80760bgtXr4_QhjhpOxNCZNQOrubva2gdXAyuj0zv3W2ApQ1GBnMJzipZB3N1rBOweZqvZ4tk-fb8MntcJppS0ic8QylhRJKKlVJzLrHWKWVZpkSppBIZMUKpSolci7ysqlxxxSmlEuXcqCpNJ-DusLft_NdgQl80NsRPaumMH0KBGRaZyAVnEX04oLrzIXSmKtrONrLbFRgVe63FP63Fj9ZirzWGr493BtWY8i_66zH9BueWeSs</recordid><startdate>201005</startdate><enddate>201005</enddate><creator>Johnson, Rory</creator><creator>Richter, Nadine</creator><creator>Jauch, Ralf</creator><creator>Gaughwin, Philip M</creator><creator>Zuccato, Chiara</creator><creator>Cattaneo, Elena</creator><creator>Stanton, Lawrence W</creator><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>7X8</scope></search><sort><creationdate>201005</creationdate><title>Human accelerated region 1 noncoding RNA is repressed by REST in Huntington's disease</title><author>Johnson, Rory ; Richter, Nadine ; Jauch, Ralf ; Gaughwin, Philip M ; Zuccato, Chiara ; Cattaneo, Elena ; Stanton, Lawrence W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-6803252a2f5dac66a1cc34588b7dbab782e7bbfb79c79dff9b6b6444a096ebf33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>3T3 Cells</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>HEK293 Cells</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Huntington Disease - genetics</topic><topic>Mice</topic><topic>Molecular Sequence Data</topic><topic>Repressor Proteins - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>RNA, Untranslated - genetics</topic><topic>RNA, Untranslated - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Johnson, Rory</creatorcontrib><creatorcontrib>Richter, Nadine</creatorcontrib><creatorcontrib>Jauch, Ralf</creatorcontrib><creatorcontrib>Gaughwin, Philip M</creatorcontrib><creatorcontrib>Zuccato, Chiara</creatorcontrib><creatorcontrib>Cattaneo, Elena</creatorcontrib><creatorcontrib>Stanton, Lawrence W</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Physiological genomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Johnson, Rory</au><au>Richter, Nadine</au><au>Jauch, Ralf</au><au>Gaughwin, Philip M</au><au>Zuccato, Chiara</au><au>Cattaneo, Elena</au><au>Stanton, Lawrence W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human accelerated region 1 noncoding RNA is repressed by REST in Huntington's disease</atitle><jtitle>Physiological genomics</jtitle><addtitle>Physiol Genomics</addtitle><date>2010-05</date><risdate>2010</risdate><volume>41</volume><issue>3</issue><spage>269</spage><epage>274</epage><pages>269-274</pages><issn>1094-8341</issn><eissn>1531-2267</eissn><abstract>In the neurons of Huntington's disease (HD) patients, gene regulatory networks are disrupted by aberrant nuclear localization of the master transcriptional repressor REST. 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| fulltext | fulltext |
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| ispartof | Physiological genomics, 2010-05, Vol.41 (3), p.269-274 |
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| language | eng |
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| source | MEDLINE; American Physiological Society; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | 3T3 Cells Animals Base Sequence HEK293 Cells HeLa Cells Humans Huntington Disease - genetics Mice Molecular Sequence Data Repressor Proteins - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism RNA, Untranslated - genetics RNA, Untranslated - metabolism |
| title | Human accelerated region 1 noncoding RNA is repressed by REST in Huntington's disease |
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