Gene silencing by synthetic U1 adaptors

Nat Biotechnol. 2009 Mar;27(3):257-63. doi: 10.1038/nbt.1525. Epub 2009 Feb 15.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Gene Expression Regulation*
  • Gene Silencing*
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Molecular Sequence Data
  • Proto-Oncogene Proteins c-raf* / genetics
  • Proto-Oncogene Proteins c-raf* / metabolism
  • RNA, Small Interfering / metabolism
  • RNA, Small Nuclear / genetics
  • RNA, Small Nuclear / metabolism*
  • Ribonucleoprotein, U1 Small Nuclear / chemical synthesis*
  • Ribonucleoprotein, U1 Small Nuclear / chemistry
  • Ribonucleoprotein, U1 Small Nuclear / metabolism*
  • Sequence Analysis, DNA
  • Transfection


  • RNA, Small Interfering
  • RNA, Small Nuclear
  • Ribonucleoprotein, U1 Small Nuclear
  • U1 small nuclear RNA
  • Luciferases
  • Proto-Oncogene Proteins c-raf

Associated data

  • GEO/GSE14434