Molecular mechanisms of RNA interference

Annu Rev Biophys. 2013:42:217-39. doi: 10.1146/annurev-biophys-083012-130404.


Small RNA molecules regulate eukaryotic gene expression during development and in response to stresses including viral infection. Specialized ribonucleases and RNA-binding proteins govern the production and action of small regulatory RNAs. After initial processing in the nucleus by Drosha, precursor microRNAs (pre-miRNAs) are transported to the cytoplasm, where Dicer cleavage generates mature microRNAs (miRNAs) and short interfering RNAs (siRNAs). These double-stranded products assemble with Argonaute proteins such that one strand is preferentially selected and used to guide sequence-specific silencing of complementary target mRNAs by endonucleolytic cleavage or translational repression. Molecular structures of Dicer and Argonaute proteins, and of RNA-bound complexes, have offered exciting insights into the mechanisms operating at the heart of RNA-silencing pathways.

Publication types

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

MeSH terms

  • Animals
  • Argonaute Proteins / chemistry
  • Argonaute Proteins / metabolism
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cytoplasm / genetics
  • Cytoplasm / metabolism
  • Gene Expression Regulation*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA Interference*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism*
  • Ribonuclease III / genetics
  • Ribonuclease III / metabolism


  • Argonaute Proteins
  • MicroRNAs
  • RNA, Small Interfering
  • Ribonuclease III