Biochemical isolation of Argonaute protein complexes by Ago-APP

Proc Natl Acad Sci U S A. 2015 Sep 22;112(38):11841-5. doi: 10.1073/pnas.1506116112. Epub 2015 Sep 8.

Abstract

During microRNA (miRNA)-guided gene silencing, Argonaute (Ago) proteins interact with a member of the TNRC6/GW protein family. Here we used a short GW protein-derived peptide fused to GST and demonstrate that it binds to Ago proteins with high affinity. This allows for the simultaneous isolation of all Ago protein complexes expressed in diverse species to identify associated proteins, small RNAs, or target mRNAs. We refer to our method as "Ago protein Affinity Purification by Peptides" (Ago-APP). Furthermore, expression of this peptide competes for endogenous TNRC6 proteins, leading to global inhibition of miRNA function in mammalian cells.

Keywords: Argonaute; GW proteins; RNAi; microRNAs; small RNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Argonaute Proteins / isolation & purification*
  • Cell Extracts
  • Chemical Precipitation
  • Chromatography, Affinity / methods*
  • Drosophila melanogaster
  • Gene Silencing
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • MicroRNAs / metabolism
  • Molecular Sequence Data
  • Multiprotein Complexes / isolation & purification*
  • Peptides / chemistry
  • Peptides / isolation & purification*

Substances

  • Argonaute Proteins
  • Cell Extracts
  • MicroRNAs
  • Multiprotein Complexes
  • Peptides

Associated data

  • GEO/GSE70553