Human accelerated region 1 noncoding RNA is repressed by REST in Huntington's disease

被引：87

作者：

Johnson, Rory ^{[1
]}

Richter, Nadine ^{[1
]}

Jauch, Ralf ^{[2
]}

Gaughwin, Philip M. ^{[1
]}

Zuccato, Chiara ^{[3
,4
]}

Cattaneo, Elena ^{[3
,4
]}

Stanton, Lawrence W. ^{[1
]}

机构：

[1] Genome Inst Singapore, Stem Cell & Dev Biol Grp, Singapore 138672, Singapore

[2] Genome Inst Singapore, Lab Struct Biochem, Singapore 138672, Singapore

[3] Univ Milan, Dept Pharmacol Sci, Milan, Italy

[4] Univ Milan, Ctr Stem Cell Res, Milan, Italy

来源：

PHYSIOLOGICAL GENOMICS | 2010年 / 41卷 / 03期

关键词：

neurodegeneration; regulation; RE1-silencing transcription factor; neuron-restrictive silencing factor; long noncoding RNA; NEUROTROPHIC FACTOR; MESSENGER-RNA; GENE; EXPRESSION;

D O I：

10.1152/physiolgenomics.00019.2010

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Johnson R, Richter N, Jauch R, Gaughwin PM, Zuccato C, Cattaneo E, Stanton LW. Human accelerated region 1 noncoding RNA is repressed by REST in Huntington's disease. Physiol Genomics 41: 269-274, 2010. First published February 23, 2010; doi:10.1152/physiolgenomics.00019.2010.-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.

引用

页码：269 / 274

页数：6

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