Photoactivated In Vivo Proximity Labeling

Curr Protoc Chem Biol. 2017 Jun 19;9(2):128-146. doi: 10.1002/cpch.18.

Abstract

Identification of molecular interactions is paramount to understanding how cells function. Most available technologies rely on co-purification of a protein of interest and its binding partners. Therefore, they are limited in their ability to detect low-affinity interactions and cannot be applied to proteins that localize to difficult-to-solubilize cellular compartments. In vivo proximity labeling (IPL) overcomes these obstacles by covalently tagging proteins and RNAs based on their proximity in vivo to a protein of interest. In IPL, a heterobifunctional probe comprising a photoactivatable moiety and biotin is recruited by a monomeric streptavidin tag fused to a protein of interest. Following UV irradiation, candidate interacting proteins and RNAs are covalently biotinylated with tight spatial and temporal control and subsequently recovered using biotin as an affinity handle. Here, we describe experimental protocols to discover novel protein-protein and protein-RNA interactions using IPL. © 2017 by John Wiley & Sons, Inc.

Keywords: noncoding RNAs; protein complexes; protein-RNA interactions; protein-protein interactions; proximity labeling; ribonucleoprotein complexes.

MeSH terms

  • Animals
  • Biotinylation
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • DNA / metabolism
  • HEK293 Cells
  • Humans
  • Jurkat Cells
  • Light*
  • Proteins / metabolism*
  • RNA / metabolism
  • Staining and Labeling / methods*
  • Streptavidin / metabolism

Substances

  • Proteins
  • RNA
  • DNA
  • Streptavidin