title: Inhibition of nonsense-mediated mRNA decay rescues the phenotype in Ullrich's disease.
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 alpha2 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 alpha2 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.
authors.affiliation: Department of Clinical Medicine, National Institute for Minamata Disease, Hama, Minamata, Japan. usuki@mind.go.jp
authors.forename: Fusako
authors.initials: F
authors.lastname: Usuki
authors.forename: Akio
authors.initials: A
authors.lastname: Yamashita
authors.forename: Itsuro
authors.initials: I
authors.lastname: Higuchi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohnishi
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Shiraishi
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Osame
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohno
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D018389:Codon, Nonsense / Q000037:antagonists & inhibitors* / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D009136:Muscular Dystrophies / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D020871:RNA Stability / Q000187:drug effects / Q000235:genetics*; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D018389:Codon, Nonsense; D002110:Caffeine; D000077191:Wortmannin