Visualizing double-stranded RNA distribution and dynamics in living cells by dsRNA binding-dependent fluorescence complementation

Virology. 2015 Nov:485:439-51. doi: 10.1016/j.virol.2015.08.023. Epub 2015 Sep 7.

Abstract

Double-stranded RNA (dsRNA) is an important type of RNA that plays essential roles in diverse cellular processes in eukaryotic organisms and a hallmark in infections by positive-sense RNA viruses. Currently, no in vivo technology has been developed for visualizing dsRNA in living cells. Here, we report a dsRNA binding-dependent fluorescence complementation (dRBFC) assay that can be used to efficiently monitor dsRNA distribution and dynamics in vivo. The system consists of two dsRNA-binding proteins, which are fused to the N- and C-terminal halves of the yellow fluorescent protein (YFP). Binding of the two fusion proteins to a common dsRNA brings the split YFP halves in close proximity, leading to the reconstitution of the fluorescence-competent structure and restoration of fluorescence. Using this technique, we were able to visualize the distribution and trafficking of the replicative RNA intermediates of positive-sense RNA viruses in living cells.

Keywords: BiFC; D-bodies; Double-stranded RNA; Fluorescent protein; Live-cell imaging; Positive-sense RNA virus; RDR6; RNA binding protein; SGS3; Viral replication complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Tracking / methods
  • Intracellular Space / metabolism
  • Luminescent Proteins / metabolism*
  • Microscopy, Confocal
  • Models, Biological
  • Protein Binding
  • Protein Transport
  • RNA, Double-Stranded / metabolism*
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • RNA-Binding Proteins / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism

Substances

  • Luminescent Proteins
  • RNA, Double-Stranded
  • RNA, Viral
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins