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- Title
Gene silencing by synthetic U1 Adaptors.
- Authors
Goraczniak, Rafal; Behlke, Mark A; Gunderson, Samuel I
- Abstract
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.
- Subjects
GENE silencing; ANTISENSE RNA; OLIGONUCLEOTIDES; EXONS (Genetics); NUCLEOPROTEINS; RNA splicing
- Publication
Nature Biotechnology, 2009, Vol 27, Issue 3, p257
- ISSN
1087-0156
- Publication type
Article
- DOI
10.1038/nbt.1525