Control of the localization and function of a miRNA silencing component TNRC6A by Argonaute protein

Nucleic Acids Res. 2015 Nov 16;43(20):9856-73. doi: 10.1093/nar/gkv1026. Epub 2015 Oct 7.

Abstract

GW182 family proteins play important roles in microRNA (miRNA)-mediated RNA silencing. They directly interact with Argonaute (Ago) proteins in processing bodies (P bodies), cytoplasmic foci involved in mRNA degradation and storage. Recently, we revealed that a human GW182 family protein, TNRC6A, is a nuclear-cytoplasmic shuttling protein, and its subcellular localization is regulated by its own nuclear localization signal and nuclear export signal. Regarding the further controlling mechanism of TNRC6A subcellular localization, we found that TNRC6A protein is tethered in P bodies by direct interaction with Ago2 under Ago2 overexpression condition in HeLa cells. Furthermore, it was revealed that such Ago proteins might be strongly tethered in the P bodies through Ago-bound small RNAs. Thus, our results indicate that TNRC6A subcellular localization is substantially controlled by the interaction with Ago proteins. Furthermore, it was also revealed that the TNRC6A subcellular localization affects the RNA silencing activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Amino Acid Motifs
  • Argonaute Proteins / metabolism*
  • Autoantigens / chemistry
  • Autoantigens / genetics
  • Autoantigens / metabolism*
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • HeLa Cells
  • Humans
  • MicroRNAs / metabolism*
  • Mutation
  • RNA Interference*
  • RNA, Small Untranslated / metabolism
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Transfection

Substances

  • AGO2 protein, human
  • Argonaute Proteins
  • Autoantigens
  • MicroRNAs
  • RNA, Small Untranslated
  • RNA-Binding Proteins
  • TNRC6A protein, human