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

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...

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Bibliographic Details
Published in:Annals of neurology 2004-05, Vol.55 (5), p.740-744
Main Authors: Usuki, Fusako, Yamashita, Akio, Higuchi, Itsuro, Ohnishi, Tetsuo, Shiraishi, Tadafumi, Osame, Mitsuhiro, Ohno, Shigeo
Format: Article
Language:English
Subjects:
Androstadienes - pharmacology
Biological and medical sciences
Caffeine - pharmacology
Codon, Nonsense - antagonists & inhibitors
Codon, Nonsense - physiology
Fibroblasts - drug effects
Fibroblasts - pathology
Frameshift Mutation
Humans
Male
Medical sciences
Muscular Dystrophies - genetics
Muscular Dystrophies - pathology
Neurology
Phenotype
RNA Stability - drug effects
RNA Stability - genetics
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Summary: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.
ISSN:0364-5134
1531-8249
DOI:10.1002/ana.20107