title: The polyglutamine-expanded protein ataxin-3 decreases bcl-2 mRNA stability.
abstract: Machado-Joseph disease/Spinocerebellar ataxia type 3 is an autosomal dominant neurodegenerative disease caused by polyglutamine-expanded ataxin-3. In this study, COS7-MJD26-GFP and COS7-MJD78-GFP cells, which were stably transfected with GFP-tagged full-length MJD gene with either 26 or 78 glutamine repeat, were used to demonstrate that both protein and mRNA levels of bcl-2 are decreased in the presence of expanded ataxin-3. However, the promoter activity in COS7-MJD78-GFP cells is much higher than that in COS7-MJD26-GFP, suggesting that the decrease of bcl-2 expression may be due to defects in mRNA stability. Therefore, 5,6-dichloro-benzimidazole 1-beta-D-ribofuranoside, an adenosine analogue to inhibit mRNA synthesis, was used to estimate the bcl-2 mRNA degradation rate. Our results demonstrated that bcl-2 mRNA decay in COS7-MJD78-GFP cells is about 3.5-fold faster than that in COS7-MJD26-GFP. Our study provides evidence, for the first time, that dysfunction of mRNA stability resulted from the presence of mutant ataxin-3.
authors.affiliation: Department of Life Science, Tunghai University, Taichung, Taiwan.
authors.forename: Chih-Liang
authors.initials: CL
authors.lastname: Tien
authors.forename: Feng-Chen
authors.initials: FC
authors.lastname: Wen
authors.forename: Mingli
authors.initials: M
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D000067699:Ataxin-3; D019556:COS Cells; D002522:Chlorocebus aethiops; D019254:Genes, bcl-2 / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010455:Peptides / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D020871:RNA Stability / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D009687:Nuclear Proteins; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D014157:Transcription Factors; C097188:polyglutamine; D000067699:Ataxin-3; C511594:Atxn3 protein, mouse