title: Human accelerated region 1 noncoding RNA is repressed by REST in Huntington's disease.
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. 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.
authors.affiliation: Stem Cell and Developmental Biology Group.
authors.forename: Rory
authors.initials: R
authors.lastname: Johnson
authors.forename: Nadine
authors.initials: N
authors.lastname: Richter
authors.forename: Ralf
authors.initials: R
authors.lastname: Jauch
authors.forename: Philip M
authors.initials: PM
authors.lastname: Gaughwin
authors.forename: Chiara
authors.initials: C
authors.lastname: Zuccato
authors.forename: Elena
authors.initials: E
authors.lastname: Cattaneo
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Stanton
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D006816:Huntington Disease / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D000099229:RE1-Silencing Transcription Factor
chemical_list: D012333:RNA, Messenger; D022661:RNA, Untranslated; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor; C000594042:HAR1 noncoding RNA, human