title: Selective silencing of mutated mRNAs in DM1 by using modified hU7-snRNAs.
abstract: We describe a function for modified human U7 small nuclear RNAs (hU7-snRNAs) distinct from modification of pre-mRNA splicing events. Engineered hU7-snRNAs containing a poly-CAG antisense sequence targeting the expanded CUG repeats of mutant DMPK transcripts in myotonic dystrophy caused specific degradation of pathogenic DMPK mRNAs without affecting the products of wild-type DMPK alleles. Abolition of the RNA gain-of-function toxicity that is responsible for pathogenesis supports the use of hU7-snRNAs for gene silencing in RNA-dominant disorders in which expanded repeats are expressed.
authors.affiliation: Université Pierre et Marie Curie-Paris6, Um76, Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: François
authors.forename: Arnaud F
authors.initials: AF
authors.lastname: Klein
authors.forename: Cyriaque
authors.initials: C
authors.lastname: Beley
authors.forename: Arnaud
authors.initials: A
authors.lastname: Jollet
authors.forename: Camille
authors.initials: C
authors.lastname: Lemercier
authors.forename: Luis
authors.initials: L
authors.lastname: Garcia
authors.forename: Denis
authors.initials: D
authors.lastname: Furling
mesh_terms: D017398:Alternative Splicing; D002478:Cells, Cultured; D042622:DNA Repeat Expansion; D020868:Gene Silencing; D005818:Genetic Engineering; D006801:Humans; D009223:Myotonic Dystrophy / Q000235:genetics; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012342:RNA, Small Nuclear / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*
chemical_list: C585517:DMPK protein, human; D012333:RNA, Messenger; D012342:RNA, Small Nuclear; C405487:U7 small nuclear RNA; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases