In vivo proximity labeling for the detection of protein-protein and protein-RNA interactions

J Proteome Res. 2014 Dec 5;13(12):6135-43. doi: 10.1021/pr500196b. Epub 2014 Oct 29.

Abstract

Accurate and sensitive detection of protein-protein and protein-RNA interactions is key to understanding their biological functions. Traditional methods to identify these interactions require cell lysis and biochemical manipulations that exclude cellular compartments that cannot be solubilized under mild conditions. Here, we introduce an in vivo proximity labeling (IPL) technology that employs an affinity tag combined with a photoactivatable probe to label polypeptides and RNAs in the vicinity of a protein of interest in vivo. Using quantitative mass spectrometry and deep sequencing, we show that IPL correctly identifies known protein-protein and protein-RNA interactions in the nucleus of mammalian cells. Thus, IPL provides additional temporal and spatial information for the characterization of biological interactions in vivo.

Keywords: Proximity labeling; RNA-seq; biotinylation; covalent tag; protein−RNA interactions; protein−protein interactions.

Publication types

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

MeSH terms

  • Biotin / chemistry
  • Biotin / metabolism
  • Chromatography, Liquid
  • Enhancer of Zeste Homolog 2 Protein
  • HEK293 Cells
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Nucleic Acid Conformation
  • Polycomb Repressive Complex 2 / chemistry
  • Polycomb Repressive Complex 2 / metabolism
  • Protein Binding
  • Protein Interaction Mapping / methods*
  • Protein Structure, Tertiary
  • RNA / chemistry
  • RNA / metabolism*
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism*
  • Sequence Analysis, RNA / methods
  • Staining and Labeling / methods*
  • Streptavidin / chemistry
  • Streptavidin / metabolism
  • Tandem Mass Spectrometry

Substances

  • RNA-Binding Proteins
  • RNA
  • Biotin
  • Streptavidin
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2

Associated data

  • GEO/GSE55370