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Inhibition of nonsense‐mediated mRNA decay rescues the phenotype in Ullrich's disease
Author(s) -
Usuki Fusako,
Yamashita Akio,
Higuchi Itsuro,
Ohnishi Tetsuo,
Shiraishi Tadafumi,
Osame Mitsuhiro,
Ohno Shigeo
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.20107
Subject(s) - nonsense mediated decay , frameshift mutation , extracellular matrix , messenger rna , downregulation and upregulation , collagen vi , translation (biology) , phenotype , microbiology and biotechnology , nonsense mutation , nonsense , mutation , gene , biology , mutant , chemistry , genetics , rna splicing , rna , missense mutation
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.