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Gene silencing by synthetic U1 Adaptors

被引：47
作者：
Goraczniak, Rafal [1 ]
Behlke, Mark A. [2 ]
Gunderson, Samuel I. [1 ]
机构：
[1] Rutgers State Univ, Piscataway, NJ 08854 USA
[2] Integrated DNA Technol, Coralville, IA 52241 USA
来源：
NATURE BIOTECHNOLOGY | 2009年 / 27卷 / 03期
基金：
美国国家卫生研究院;
关键词：
PRE-MESSENGER-RNA; LOCKED NUCLEIC-ACIDS; ANTISENSE OLIGONUCLEOTIDES; MAMMALIAN-CELLS; POLY(A) POLYMERASE; MODIFIED SIRNAS; RAF KINASE; IN-VIVO; EXPRESSION; POLYADENYLATION;
D O I：
10.1038/nbt.1525
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
We describe a gene silencing method that employs a mechanism of action distinct from those of antisense and RNA interference. U1 Adaptors are bifunctional oligonucleotides with a 'target domain' complementary to a site in the target gene's terminal exon and a 'U1 domain' that binds to the U1 small nuclear RNA component of the U1 small nuclear ribonucleoprotein (U1 snRNP) splicing factor. Tethering of U1 snRNP to the target pre-mRNA inhibits poly(A)-tail addition, causing degradation of that RNA species in the nucleus. U1 Adaptors can inhibit both endogenous and reporter genes in a sequence-specific manner. Comparison of U1 Adaptors with small interfering RNA (siRNA) using a genome-wide microarray analysis indicates that U1 Adaptors have limited off-target effects and no detectable adverse effects on splicing. Further, targeting the same gene either with multiple U1 Adaptors or with a U1 Adaptor and siRNA strongly enhances gene silencing.
引用
收藏
页码：257 / 263
页数：7
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