The Bifunctional microRNA miR-9/miR-9*Regulates REST and CoREST and Is Downregulated in Huntington's Disease

被引:536
作者
Packer, Amy N. [1 ,5 ]
Xing, Yi [1 ,4 ]
Harper, Scott Q. [6 ]
Jones, Lesley [7 ,8 ]
Davidson, Beverly L. [1 ,2 ,3 ,5 ]
机构
[1] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA
[2] Univ Iowa, Dept Mol Physiol & Biophys, Iowa City, IA 52242 USA
[3] Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA
[4] Univ Iowa, Dept Biomed Engn, Iowa City, IA 52242 USA
[5] Univ Iowa, Program Mol & Cellular Biol, Iowa City, IA 52242 USA
[6] Ohio State Univ, Dept Pediat, Columbus, OH 43205 USA
[7] Cardiff Univ, Wales Sch Med, Dept Psychol Med, Cardiff CF14 4XN, S Glam, Wales
[8] Cardiff Univ, Wales Sch Med, Inst Med Genet, Cardiff CF14 4XN, S Glam, Wales
基金
美国国家卫生研究院;
关键词
miRNA; REST; Huntington's disease; cortex; coordination; RNA interference;
D O I
10.1523/JNEUROSCI.2390-08.2008
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The transcription factor REST silences neuronal gene expression in non-neuronal cells. In neurons, the protein is sequestered in the cytoplasm in part through binding to huntingtin. Polyglutamine expansions in huntingtin, which causes Huntington's disease (HD), abrogates REST-huntingtin binding. Consequently, REST translocates to the nucleus, occupies RE1 repressor sequences and decreases neuronal gene expression. In this work, we found that levels of several microRNAs (miRNAs) with upstream RE1 sites are decreased in HD patient cortices relative to healthy controls. Interestingly, one of these, the bifunctional brain enriched miR-9/miR-9*, targets two components of the REST complex: miR-9 targets REST and miR-9* targets CoREST. These data provide evidence for a double negative feedback loop between the REST silencing complex and the miRNAs it regulates.
引用
收藏
页码:14341 / 14346
页数:6
相关论文
共 29 条
[1]   CoREST:: A functional corepressor required for regulation of neural-specific gene expression [J].
Andrés, ME ;
Burger, C ;
Peral-Rubio, MJ ;
Battaglioli, E ;
Anderson, ME ;
Grimes, J ;
Dallman, J ;
Ballas, N ;
Mandel, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (17) :9873-9878
[2]   REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis [J].
Ballas, N ;
Grunseich, C ;
Lu, DD ;
Speh, JC ;
Mandel, G .
CELL, 2005, 121 (04) :645-657
[3]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[4]   Genome-wide analysis of repressor element 1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) target genes [J].
Bruce, AW ;
Donaldson, IJ ;
Wood, IC ;
Yerbury, SA ;
Sadowski, MI ;
Chapman, M ;
Göttgens, B ;
Buckley, NJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (28) :10458-10463
[5]   Reciprocal actions of REST and a microRNA promote neuronal identity [J].
Conaco, C ;
Otto, S ;
Han, JJ ;
Mandel, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (07) :2422-2427
[6]   Regional and cellular gene expression changes in human Huntington's disease brain [J].
Hodges, A ;
Strand, AD ;
Aragaki, AK ;
Kuhn, A ;
Sengstag, T ;
Hughes, G ;
Elliston, LA ;
Hartog, C ;
Goldstein, DR ;
Thu, D ;
Hollingsworth, ZR ;
Collin, F ;
Synek, B ;
Holmans, PA ;
Young, AB ;
Wexler, NS ;
Delorenzi, M ;
Kooperberg, C ;
Augood, SJ ;
Faull, RLM ;
Olson, JM ;
Jones, L ;
Luthi-Carter, R .
HUMAN MOLECULAR GENETICS, 2006, 15 (06) :965-977
[7]   A microRNA-based gene dysregulation pathway in Huntington's disease [J].
Johnson, Rory ;
Zuccato, Chiara ;
Belyaev, Nikolai D. ;
Guest, Deborah J. ;
Cattaneo, Elena ;
Buckley, Noel J. .
NEUROBIOLOGY OF DISEASE, 2008, 29 (03) :438-445
[8]   Genome-wide identification of in vivo protein-DNA binding sites from ChIP-Seq data [J].
Jothi, Raja ;
Cuddapah, Suresh ;
Barski, Artem ;
Cui, Kairong ;
Zhao, Keji .
NUCLEIC ACIDS RESEARCH, 2008, 36 (16) :5221-5231
[9]   A microRNA feedback circuit in midbrain dopamine neurons [J].
Kim, Jongpil ;
Inoue, Keiichi ;
Ishii, Jennifer ;
Vanti, William B. ;
Voronov, Sergey V. ;
Murchison, Elizabeth ;
Hannon, Gregory ;
Abeliovich, Asa .
SCIENCE, 2007, 317 (5842) :1220-1224
[10]   Homeostatic regulation of MeCP2 expression by a CREB-induced microRNA [J].
Klein, Matthew E. ;
Lioy, Daniel T. ;
Ma, Lin ;
Impey, Soren ;
Mandel, Gail ;
Goodman, Richard H. .
NATURE NEUROSCIENCE, 2007, 10 (12) :1513-1514