Long CGG-repeat tracts are toxic to human cells: Implications for carriers of Fragile X premutation alleles

被引：47

作者：

Handa, V

Goldwater, D

Stiles, D

Cam, M

Poy, G

Kumari, D

Usdin, K

机构：

[1] NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA

[2] NIDDKD, Microarray Core Facil, NIH, Bethesda, MD 20892 USA

来源：

FEBS LETTERS | 2005年 / 579卷 / 12期

关键词：

fragile X syndrome; CGG-repeat; premutation; POF; fragile X tremor and ataxia syndrome;

D O I：

10.1016/j.febslet.2005.04.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

People with 59-200 CGG (.) CCG-repeats in the 5' UTR of one of their FMR1 genes are at risk for Fragile X tremor and ataxia syndrome. Females are also at risk for premature ovarian failure. These symptoms are thought to be due to the presence of the repeats at the DNA and/or RNA level. We show here that long transcribed but untranslated CGG-repeat tracts are toxic to human cells and alter the expression of a wide variety of different genes including caspase-8, CYFIP, Neurotensin and UBE3A. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

收藏

页码：2702 / 2708

页数：7

相关论文

共 35 条

[21] Linkage disequilibrium at the Angelman syndrome gene UBE3A in autism families [J].

Nurmi, EL ;

Bradford, Y ;

Chen, YH ;

Hall, J ;

Arnone, B ;

Gardiner, MB ;

Hutcheson, HB ;

Gilbert, JR ;

Pericak-Vance, MA ;

Copeland-Yates, SA ;

Michaelis, RC ;

Wassink, TH ;

Santangelo, SL ;

Sheffield, VC ;

Piven, J ;

Folstein, SE ;

Haines, JL ;

Sutcliffe, JS .

GENOMICS, 2001, 77 (1-2) :105-113

[22] A fragile balance: FMR1 expression levels [J].

Oostra, BA ;

Willemsen, R .

HUMAN MOLECULAR GENETICS, 2003, 12 :R249-R257

[23] CYFIP/Sra-1 controls neuronal connectivity in Drosophila and links the Rac1 GTPase pathway to the fragile X protein [J].

Schenck, A ;

Bardoni, B ;

Langmann, C ;

Harden, N ;

Mandel, JL ;

Giangrande, A .

NEURON, 2003, 38 (06) :887-898

[24] Preferential transformation of human neuronal cells by human adenoviruses and the origin of HEK 293 cells [J].

Shaw, G ;

Morse, S ;

Ararat, M ;

Graham, FL .

FASEB JOURNAL, 2002, 16 (06) :869-+

[25]

Sherman SL, 2000, AM J MED GENET, V97, P189, DOI 10.1002/1096-8628(200023)97:3<189::AID-AJMG1036>3.0.CO

[26]

2-J

[27] Decreased cAMP response element-mediated transcription - An early event in exon 1 and full-length cell models of Huntington's disease that contributes to polyglutamine pathogenesis [J].

Sugars, KL ;

Brown, R ;

Cook, LJ ;

Swartz, J ;

Rubinsztein, DC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (06) :4988-4999

[28] Elevated levels of FMR1 mRNA in carrier males:: A new mechanism of involvement in the fragile-X syndrome [J].

Tassone, F ;

Hagerman, RJ ;

Taylor, AK ;

Gane, LW ;

Godfrey, TE ;

Hagerman, PJ .

AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 66 (01) :6-15

[29] Parkin facilitates the elimination of expanded polyglutamine proteins and leads to preservation of proteasome function [J].

Tsai, YC ;

Fishman, PS ;

Thakor, NV ;

Oyler, GA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (24) :22044-22055

[30] Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease [J].

Turmaine, M ;

Raza, A ;

Mahal, A ;

Mangiarini, L ;

Bates, GP ;

Davies, SW .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (14) :8093-8097

← 1 2 3 4 →