Inhibition of nonsense‐mediated mRNA decay rescues the phenotype in Ullrich's disease

F Usuki, A Yamashita, I Higuchi… - Annals of Neurology …, 2004 - Wiley Online Library
F Usuki, A Yamashita, I Higuchi, T Ohnishi, T Shiraishi, M Osame, S Ohno
Annals of Neurology: Official Journal of the American Neurological …, 2004Wiley Online Library
Nonsense‐mediated mRNA decay (NMD) is an mRNA surveillance system that eliminates
aberrant mRNAs containing premature translation termination codons (PTCs). We evaluated
the role of NMD in of Ullrich's disease. The patient has a frameshift mutation with a PTC in
the collagen VI α2 gene causing the loss of collagen VI and functional defects in
extracellular matrix (ECM). The pharmacological block of NMD caused upregulation of the
mutant collagen VI α2 subunit, resulting in collagen VI assembly and partially functional …
Abstract
Nonsense‐mediated mRNA decay (NMD) is an mRNA surveillance system that eliminates aberrant mRNAs containing premature translation termination codons (PTCs). We evaluated the role of NMD in of Ullrich's disease. The patient has a frameshift mutation with a PTC in the collagen VI α2 gene causing the loss of collagen VI and functional defects in extracellular matrix (ECM). The pharmacological block of NMD caused upregulation of the mutant collagen VI α2 subunit, resulting in collagen VI assembly and partially functional ECM formation. Our results suggest that NMD inhibitors can be used as a therapeutic tool to rescue some human genetic diseases exacerbated by NMD.
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