Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells

Nature. 2001 May 24;411(6836):494-8. doi: 10.1038/35078107.


RNA interference (RNAi) is the process of sequence-specific, post-transcriptional gene silencing in animals and plants, initiated by double-stranded RNA (dsRNA) that is homologous in sequence to the silenced gene. The mediators of sequence-specific messenger RNA degradation are 21- and 22-nucleotide small interfering RNAs (siRNAs) generated by ribonuclease III cleavage from longer dsRNAs. Here we show that 21-nucleotide siRNA duplexes specifically suppress expression of endogenous and heterologous genes in different mammalian cell lines, including human embryonic kidney (293) and HeLa cells. Therefore, 21-nucleotide siRNA duplexes provide a new tool for studying gene function in mammalian cells and may eventually be used as gene-specific therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Nuclear
  • COS Cells
  • Cell Cycle Proteins
  • Cells, Cultured
  • Cnidaria
  • Coleoptera
  • Drosophila
  • Gene Silencing*
  • Genes / physiology*
  • Genes, Reporter
  • Genetic Techniques
  • HeLa Cells
  • Humans
  • Lamins
  • Nuclear Matrix-Associated Proteins
  • Nuclear Proteins / genetics
  • Nucleic Acid Hybridization
  • RNA, Double-Stranded / pharmacology*
  • RNA, Messenger / antagonists & inhibitors*
  • RNA, Messenger / metabolism
  • Vimentin / genetics


  • Antigens, Nuclear
  • Cell Cycle Proteins
  • Lamins
  • NUMA1 protein, human
  • Nuclear Matrix-Associated Proteins
  • Nuclear Proteins
  • RNA, Double-Stranded
  • RNA, Messenger
  • Vimentin