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Sequence‐dependent and independent inhibition specific for mutant ataxin‐3 by small interfering RNA
Author(s) -
Li Yi,
Yokota Takanori,
Matsumura Ryusuke,
Taira Kazunari,
Mizusawa Hidehiro
Publication year - 2004
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20141
Subject(s) - mutant , small interfering rna , allele , wild type , biology , rna , microbiology and biotechnology , gene , genetics
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. Ann Neurol 2004;56:124–129