miR-19, miR-101 and miR-130 co-regulate ATXN1 levels to potentially modulate SCA1 pathogenesis

被引：178

作者：

Lee, Yoontae ^{[1
,4
]}

Samaco, Rodney C. ^{[1
]}

Gatchel, Jennifer R. ^{[2
]}

Thaller, Christina ^{[3
]}

Orr, Harry T. ^{[5
]}

Zoghbi, Huda Y. ^{[1
,2
,3
,4
]}

机构：

[1] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[2] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA

[3] Baylor Coll Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA

[4] Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA

[5] Univ Minnesota, Dept Biochem Biophys & Mol Biol, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA

来源：

NATURE NEUROSCIENCE | 2008年 / 11卷 / 10期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/nn.2183

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Spinocerebellar ataxia type 1 is caused by expansion of a translated CAG repeat in ataxin1 (ATXN1). The level of the polyglutamine-expanded protein is one of the factors that contributes to disease severity. Here we found that miR-19, miR-101 and miR-130 co-regulate ataxin1 levels and that their inhibition enhanced the cytotoxicity of polyglutamine-expanded ATXN1 in human cells. We provide a new candidate mechanism for modulating the pathogenesis of neurodegenerative diseases sensitive to protein dosage.

引用

页码：1137 / 1139

页数：3

共 15 条

[1] IDENTIFICATION AND CHARACTERIZATION OF THE GENE CAUSING TYPE-1 SPINOCEREBELLAR ATAXIA [J].

BANFI, S ;

SERVADIO, A ;

CHUNG, MY ;

KWIATKOWSKI, TJ ;

MCCALL, AE ;

DUVICK, LA ;

SHEN, Y ;

ROTH, EJ ;

ORR, HT ;

ZOGHBI, HY .

NATURE GENETICS, 1994, 7 (04) :513-520

[2] 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

[3] SCA1 TRANSGENIC MICE - A MODEL FOR NEURODEGENERATION CAUSED BY AN EXPANDED CAG TRINUCLEOTIDE REPEAT [J].

BURRIGHT, EN ;

CLARK, HB ;

SERVADIO, A ;

MATILLA, T ;

FEDDERSEN, RM ;

YUNIS, WS ;

DUVICK, LA ;

ZOGHBI, HY ;

ORR, HT .

CELL, 1995, 82 (06) :937-948

[4] YAC transgenic mice carrying pathological alleles of the MJD1 locus exhibit a mild and slowly progressive cerebellar deficit [J].

Cemal, CK ;

Carroll, CJ ;

Lawrence, L ;

Lowrie, MB ;

Ruddle, P ;

Al-Mahdawi, S ;

King, RHM ;

Pook, MA ;

Huxley, C ;

Chamberlain, S .

HUMAN MOLECULAR GENETICS, 2002, 11 (09) :1075-1094

[5]

Clark HB, 1997, J NEUROSCI, V17, P7385

[6] Nuclear localization or inclusion body formation of ataxin-2 are not necessary for SCA2 pathogenesis in mouse or human [J].

Huynh, DP ;

Figueroa, K ;

Hoang, N ;

Pulst, SM .

NATURE GENETICS, 2000, 26 (01) :44-50

[7] Combinatorial microRNA target predictions [J].

Krek, A ;

Grun, D ;

Poy, MN ;

Wolf, R ;

Rosenberg, L ;

Epstein, EJ ;

MacMenamin, P ;

da Piedade, I ;

Gunsalus, KC ;

Stoffel, M ;

Rajewsky, N .

NATURE GENETICS, 2005, 37 (05) :495-500

[8] Prediction of mammalian microRNA targets [J].

Lewis, BP ;

Shih, IH ;

Jones-Rhoades, MW ;

Bartel, DP ;

Burge, CB .

CELL, 2003, 115 (07) :787-798

[9] Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1 [J].

Lim, Janghoo ;

Crespo-Barreto, Juan ;

Jafar-Nejad, Paymaan ;

Bowman, Aaron B. ;

Richman, Ronald ;

Hill, David E. ;

Orr, Harry T. ;

Zoghbi, Huda Y. .

NATURE, 2008, 452 (7188) :713-U1

[10] Trinucleotide repeat disorders [J].

Orr, Harry T. ;

Zoghbi, Huda Y. .

ANNUAL REVIEW OF NEUROSCIENCE, 2007, 30 :575-621

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