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.
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