Ribonuclease dicer cleaves triplet repeat hairpins into shorter repeats that silence specific targets

被引：152

作者：

Krol, Jacelk ^{[1
]}

Fiszer, Agnieszka ^{[1
]}

Mykowska, Agnieszka ^{[1
]}

Sobczak, Krzysztof ^{[1
]}

de Mezer, Mateusz ^{[1
]}

Krzyzosiak, Wlodzimierz J. ^{[1
]}

机构：

[1] Polish Acad Sci, Inst Bioorgan Chem, Lab Canc Genet, Noskowskiego 12-14, PL-61704 Poznan, Poland

来源：

MOLECULAR CELL | 2007年 / 25卷 / 04期

关键词：

D O I：

10.1016/j.molcel.2007.01.031

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：

Ribonuclease Dicer functions in cells to excise microRNAs from their precursors and process long double-stranded RNAs into short interfering RNAs. We show that transcripts containing long hairpin structures composed of CNG repeats are another class of Dicer targets. The cellular levels of transcripts from mutant genes involved in triplet repeat expansion diseases such as myotonic dystrophy type 1, Huntington's disease, and spinocerebellar ataxia type 1 are under Dicer control. The Dicer-induced downregulation of the mutant transcript in myotonic dystrophy cells is accompanied by the downregulation of transcripts containing long complementary repeats. Short CUG repeats generated from long repeat hairpins act as siRNAs and use the RNA interference pathway to trigger the downstream silencing effects. We demonstrate that synthetic oligonucleotides composed of repeats are highly specific in the silencing of mutant transcripts containing complementary repeats and may be considered as potential therapeutic agents.

引用

页码：575 / 586

页数：12

共 38 条

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