Sequence-dependent and independent inhibition specific for mutant ataxin-3 by small interfering RNA
| Autor: | Yi Li, Takanori Yokota, Ryusuke Matsumura, Hidehiro Mizusawa, Kazunari Taira |
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| Rok vydání: | 2004 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Small interfering RNA Molecular Sequence Data Mutant Nerve Tissue Proteins Biology Trinucleotide Repeats Humans RNA Small Interfering Allele Ataxin-3 Gene Protein secondary structure Cells Cultured Polymorphism Genetic Base Sequence Wild type Nuclear Proteins RNA Machado-Joseph Disease Molecular biology Repressor Proteins Neurology Ataxin Mutation Neurology (clinical) |
| Zdroj: | Annals of Neurology. 56:124-129 |
| ISSN: | 1531-8249 0364-5134 |
| DOI: | 10.1002/ana.20141 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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