Human Argonaute 2 Has Diverse Reaction Pathways on Target RNAs

Mol Cell. 2015 Jul 2;59(1):117-24. doi: 10.1016/j.molcel.2015.04.027.


Argonaute is a key enzyme of various RNA silencing pathways. We use single-molecule fluorescence measurements to characterize the reaction mechanisms of the core-RISC (RNA-induced silencing complex) composed of human Argonaute 2 and a small RNA. We found that target binding of core-RISC starts at the seed region, resulting in four distinct reaction pathways: target cleavage, transient binding, stable binding, and Argonaute unloading. The target cleavage requires extensive sequence complementarity and dramatically accelerates core-RISC recycling. The stable binding of core-RISC is efficiently established with the seed match only, providing a potential explanation for the seed-match rule of miRNA (microRNA) target selection. Target cleavage on perfect-match targets sensitively depends on RNA sequences, providing an insight into designing more efficient siRNAs (small interfering RNAs).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Argonaute Proteins / metabolism*
  • Base Sequence
  • Fluorescence
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism
  • RNA-Induced Silencing Complex / genetics*
  • RNA-Induced Silencing Complex / metabolism


  • AGO2 protein, human
  • Argonaute Proteins
  • MicroRNAs
  • RNA, Small Interfering
  • RNA-Induced Silencing Complex