Quantifying RNA-protein interactions in situ using modified-MTRIPs and proximity ligation

Nucleic Acids Res. 2013 Jan 7;41(1):e12. doi: 10.1093/nar/gks837. Epub 2012 Sep 4.

Abstract

The stabilization, translation and degradation of RNA are regulated by interactions between trans-acting factors, such as microRNA and RNA-binding proteins (RBP). In order to investigate the relationships between these events and their significance, a method that detects the localization of these interactions within a single cell, as well as their variability across a cell population, is needed. To visualize and quantify RNA-protein interactions in situ, we developed a proximity ligation assay (PLA) that combined peptide-modified, multiply-labelled tetravalent RNA imaging probes (MTRIPs), targeted to sequences near RBP binding sites, with proximity ligation and rolling circle amplification (RCA). Using this method, we detected and quantified, with single-interaction sensitivity, the localization and frequency of interactions of the human respiratory syncytial virus (hRSV) nucleocapsid protein (N) with viral genomic RNA (gRNA). We also described the effects of actinomycin D (actD) on the interactions of HuR with β-actin mRNA and with poly(A)+ mRNA at both native and increased HuR expression levels.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line
  • Dactinomycin / pharmacology
  • ELAV Proteins / metabolism
  • Humans
  • Microscopy, Fluorescence
  • Molecular Imaging / methods*
  • Molecular Probes / chemistry
  • Nucleocapsid Proteins / metabolism
  • Oligopeptides
  • Peptides / chemistry
  • RNA / metabolism*
  • RNA, Messenger / metabolism
  • RNA, Viral / metabolism
  • RNA-Binding Proteins / metabolism*

Substances

  • ELAV Proteins
  • Molecular Probes
  • Nucleocapsid Proteins
  • Oligopeptides
  • Peptides
  • RNA, Messenger
  • RNA, Viral
  • RNA-Binding Proteins
  • Dactinomycin
  • RNA
  • FLAG peptide