title: RNA-binding proteins hnRNP A2/B1 and CUGBP1 suppress fragile X CGG premutation repeat-induced neurodegeneration in a Drosophila model of FXTAS.
abstract: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a recently described neurodegenerative disorder of older adult carriers of premutation alleles (60-200 CGG repeats) in the fragile X mental retardation gene (FMR1). It has been proposed that FXTAS is an RNA-mediated neurodegenerative disease caused by the titration of RNA-binding proteins by the CGG repeats. To test this hypothesis, we utilize a transgenic Drosophila model of FXTAS that expresses a premutation-length repeat (90 CGG repeats) from the 5' UTR of the human FMR1 gene and displays neuronal degeneration. Here, we show that overexpression of RNA-binding proteins hnRNP A2/B1 and CUGBP1 suppresses the phenotype of the CGG transgenic fly. Furthermore, we show that hnRNP A2/B1 directly interacts with riboCGG repeats and that the CUGBP1 protein interacts with the riboCGG repeats via hnRNP A2/B1.
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors: Oyinkan A
authors: OA
authors: Sofola
authors: Peng
authors: P
authors: Jin
authors: Yunlong
authors: Y
authors: Qin
authors: Ranhui
authors: R
authors: Duan
authors: Huijie
authors: H
authors: Liu
authors: Maria
authors: M
authors: de Haro
authors: David L
authors: DL
authors: Nelson
authors: Juan
authors: J
authors: Botas
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000067879:CELF1 Protein; D004195:Disease Models, Animal; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005123:Eye / Q000473:pathology / Q000648:ultrastructure; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005600:Fragile X Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics / Q000378:metabolism*; D047468:Immunoprecipitation / Q000379:methods; D008855:Microscopy, Electron, Scanning / Q000379:methods; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
chemical_list: D000067879:CELF1 Protein; D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D016601:RNA-Binding Proteins; C102843:CELF1 protein, human
references: Brain. 2006 Jan;129(Pt 1):256-71
references: 16246864
references: RNA Biol. 2006 Jan-Mar;3(1):28-35
references: 17114940
references: Annu Rev Neurosci. 2006;29:259-77
references: 16776586
references: Hum Mol Genet. 2006 Jul 1;15(13):2138-45
references: 16723374
references: Brain. 2006 Jan;129(Pt 1):243-55
references: 16332642
references: Am J Hum Genet. 2000 Jan;66(1):6-15
references: 10631132
references: Biochem Biophys Res Commun. 2000 Oct 22;277(2):518-23
references: 11032753
references: J Biol Chem. 2001 Mar 16;276(11):7820-6
references: 11124939
references: Neurology. 2001 Jul 10;57(1):127-30
references: 11445641
references: Curr Opin Genet Dev. 2002 Jun;12(3):278-83
references: 12076670
references: Brain. 2002 Aug;125(Pt 8):1760-71
references: 12135967
references: Hum Mol Genet. 2003 May 1;12(9):949-59
references: 12700164
references: Neuron. 2003 Aug 28;39(5):739-47
references: 12948442
references: Science. 2003 Dec 12;302(5652):1978-80
references: 14671308
references: J Biol Chem. 2004 Mar 26;279(13):13129-39
references: 14722059
references: Am J Hum Genet. 2004 May;74(5):805-16
references: 15052536
references: Am J Hum Genet. 2004 May;74(5):793-804
references: 15065017
references: Mol Biol Cell. 1996 Jul;7(7):1059-73
references: 8862520
references: Nucleic Acids Res. 1996 Nov 15;24(22):4407-14
references: 8948631
references: Biochem Biophys Res Commun. 1999 Jun 24;260(1):17-22
references: 10381337
references: Hum Mol Genet. 2005 Dec 1;14(23):3661-71
references: 16239243
references: RNA Biol. 2004 Jul;1(2):103-5
references: 17179750
references: Neuron. 2007 Aug 16;55(4):556-64
references: 17698009