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Specific and potent RNAi in the nucleus of human cells

Nat Struct Mol Biol. 2005 Feb;12(2):133-7. doi: 10.1038/nsmb886. Epub 2005 Jan 9.

Abstract

RNA interference (RNAi) has become a research tool to control gene expression in various organisms and holds potential as a new therapeutic strategy. The mechanism of small interfering RNA (siRNA)-mediated RNAi involves target mRNA cleavage and destruction in the cytoplasm. We investigated siRNA-mediated induction of RNAi in the nucleus of human cells. Notably, we observed highly efficient knockdown of small nuclear RNA 7SK by siRNA. siRNA- and microRNA-programmed RNA-induced silencing complexes (RISCs) were present in both cytoplasmic and nuclear compartments and specifically cleaved their perfectly matched target RNA with markedly high efficiencies. Our results provide the first evidence that human RISCs programmed with siRNA are present in the nucleus and can knock down target RNA levels. These studies reveal new roles for the RNAi machinery in modulating post-transcriptional gene expression in the nucleus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Nucleus / genetics*
  • Cell Nucleus / metabolism
  • HeLa Cells
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • RNA Interference*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Sensitivity and Specificity
  • Substrate Specificity

Substances

  • MicroRNAs
  • RNA, Small Interfering