Reduced Expression of Argonaute 1, Argonaute 2, and TRBP Changes Levels and Intracellular Distribution of RNAi Factors

Sci Rep. 2015 Aug 5:5:12855. doi: 10.1038/srep12855.

Abstract

Until recently, Argonaute 2 (AGO2) and other RNA factors were believed to be restricted to the cytoplasm of mammalian somatic cells. It is now becoming appreciated that RNAi factors can also be found in cell nuclei, but much remains to be learned about their transport, molecular recognition, and function. We find that siRNA-mediated reduction of AGO1 or AGO2 increases the proportion of AGO1 or AGO2 in cell nuclei. Inhibition of AGO1 expression led to increased AGO2 levels, while knockdown of AGO2 led to increased levels of AGO1. Blocking AGO1, AGO2, or TRBP expression changed expression levels and nuclear distribution of RNAi factors Dicer, TNRC6A (GW182), and TRBP. These data reveal the expression of RNAi proteins is mutually dependent and that perturbation can affect subcellular distribution of those factors inside cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism*
  • Autoantigens / metabolism
  • Cell Line, Tumor
  • Cell Nucleus / enzymology
  • DEAD-box RNA Helicases / metabolism
  • Eukaryotic Initiation Factors / genetics
  • Eukaryotic Initiation Factors / metabolism*
  • Gene Knockdown Techniques
  • Humans
  • Protein Transport
  • RNA Interference
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Ribonuclease III / metabolism

Substances

  • AGO1 protein, human
  • AGO2 protein, human
  • Argonaute Proteins
  • Autoantigens
  • Eukaryotic Initiation Factors
  • RNA-Binding Proteins
  • TNRC6A protein, human
  • trans-activation responsive RNA-binding protein
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases