title: Sequence-dependent and independent inhibition specific for mutant ataxin-3 by small interfering RNA.
abstract: In Machado-Joseph disease (MJD) gene, there is a C/G polymorphism immediately after the CAG repeat; the expanded CAG repeat tract is exclusively followed by C, whereas about half of wild-type alleles are followed by G. Using this C/G polymorphism, we have engineered the small interfering RNA (siRNA) which decreased the expression of mutant ataxin-3, Q79C, by 96.0%, whereas there was minimal reduction on that of the wild type, Q22G (5.9%). Furthermore, unexpectedly, the expression of another wild-type allele, Q22C, was also much less suppressed (22.5%) by this siRNA possibly due to difference of the secondary structure of the target RNA. This is the first report of sequence-independent discrimination of mutant and wild-type alleles by siRNA.
authors.affiliation: Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Takanori
authors.initials: T
authors.lastname: Yokota
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Matsumura
authors.forename: Kazunari
authors.initials: K
authors.lastname: Taira
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Mizusawa
mesh_terms: D000067699:Ataxin-3; D001483:Base Sequence; D002478:Cells, Cultured; D006801:Humans; D017827:Machado-Joseph Disease / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins; D011110:Polymorphism, Genetic; D012313:RNA / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins; D018911:Trinucleotide Repeats
chemical_list: D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D012313:RNA; C092341:ATXN3 protein, human; D000067699:Ataxin-3