Selective silencing of mutated mRNAs in DM1 by using modified hU7-snRNAs

被引：64

作者：

Francois, Virginie ^{[1
,2
,3
,4
]}

Klein, Arnaud F. ^{[1
,2
,3
,4
]}

Beley, Cyriaque ^{[1
,2
,3
,4
]}

Jollet, Arnaud ^{[1
,2
,3
,4
]}

Lemercier, Camille ^{[1
,2
,3
,4
]}

Garcia, Luis ^{[1
,2
,3
,4
]}

Furling, Denis ^{[1
,2
,3
,4
]}

机构：

[1] Univ Paris 06, Um76, Paris, France

[2] CNRS, UMR 7215, Paris, France

[3] INSERM, U974, Paris, France

[4] Inst Myol, Paris, France

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2011年 / 18卷 / 01期

关键词：

MYOTONIC-DYSTROPHY; U7; SNRNA; REPEAT; EXPANSION; REVERSAL; DMPK; EXON;

D O I：

10.1038/nsmb.1958

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：85 / 87

页数：3

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