Why Argonaute is needed to make microRNA target search fast and reliable

Semin Cell Dev Biol. 2017 May:65:20-28. doi: 10.1016/j.semcdb.2016.05.017. Epub 2016 May 26.

Abstract

MicroRNA (miRNA) interferes with the translation of cognate messenger RNA (mRNA) by finding, preferentially binding, and marking it for degradation. To facilitate the search process, Argonaute (Ago) proteins come together with miRNA, forming a dynamic search complex. In this review we use the language of free-energy landscapes to discuss recent single-molecule and high-resolution structural data in the light of theoretical work appropriated from the study of transcription-factor search. We suggest that experimentally observed internal states of the Ago-miRNA search complex may have the explicit biological function of speeding up search while maintaining specificity.

Keywords: Argonaute; FRET; Free-energy landscape; Lateral diffusion; MicroRNA target prediction; RNA silencing; Search stability paradox; Single molecule; Target Search; Theoretical model; miRNA.

Publication types

  • Review

MeSH terms

  • Argonaute Proteins / chemistry*
  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism
  • Binding Sites
  • Diffusion
  • Fluorescence Resonance Energy Transfer
  • Gene Expression Regulation*
  • Humans
  • MicroRNAs / chemistry*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Protein Binding
  • Protein Conformation
  • RNA Stability
  • RNA, Messenger / chemistry*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Thermodynamics

Substances

  • AGO2 protein, human
  • Argonaute Proteins
  • MicroRNAs
  • RNA, Messenger