Functional siRNAs and miRNAs exhibit strand bias

Cell. 2003 Oct 17;115(2):209-16. doi: 10.1016/s0092-8674(03)00801-8.


Both microRNAs (miRNA) and small interfering RNAs (siRNA) share a common set of cellular proteins (Dicer and the RNA-induced silencing complex [RISC]) to elicit RNA interference. In the following work, a statistical analysis of the internal stability of published miRNA sequences in the context of miRNA precursor hairpins revealed enhanced flexibility of miRNA precursors, especially at the 5'-anti-sense (AS) terminal base pair. The same trend was observed in siRNA, with functional duplexes displaying a lower internal stability (Delta0.5 kcal/mol) at the 5'-AS end than nonfunctional duplexes. Average internal stability of siRNA molecules retrieved from plant cells after introduction of long RNA sequences also shows this characteristic thermodynamic signature. Together, these results suggest that the thermodynamic properties of siRNA play a critical role in determining the molecule's function and longevity, possibly biasing the steps involved in duplex unwinding and strand retention by RISC.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Base Pair Mismatch
  • Base Pairing
  • Base Sequence
  • Caenorhabditis elegans / genetics
  • Cell Line
  • Drosophila / genetics
  • Gene Silencing
  • Humans
  • Mice
  • MicroRNAs / chemistry
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Models, Biological
  • Proteins / genetics
  • RNA Precursors / chemistry
  • RNA Precursors / genetics
  • RNA Precursors / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Plant / genetics
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism*
  • Thermodynamics


  • MicroRNAs
  • Proteins
  • RNA Precursors
  • RNA, Messenger
  • RNA, Plant
  • RNA, Small Interfering