G3BP1 Promotes Stress-Induced RNA Granule Interactions to Preserve Polyadenylated mRNA

J Cell Biol. 2015 Apr 13;209(1):73-84. doi: 10.1083/jcb.201408092. Epub 2015 Apr 6.

Abstract

G3BP1, a target of TDP-43, is required for normal stress granule (SG) assembly, but the functional consequences of failed SG assembly remain unknown. Here, using both transformed cell lines and primary neurons, we investigated the functional impact of this disruption in SG dynamics. While stress-induced translational repression and recruitment of key SG proteins was undisturbed, depletion of G3BP1 or its upstream regulator TDP-43 disturbed normal interactions between SGs and processing bodies (PBs). This was concomitant with decreased SG size, reduced SG-PB docking, and impaired preservation of polyadenylated mRNA. Reintroduction of G3BP1 alone was sufficient to rescue all of these phenotypes, indicating that G3BP1 is essential for normal SG-PB interactions and SG function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / physiology*
  • Cytoplasmic Granules / metabolism
  • DNA Helicases
  • DNA-Binding Proteins / metabolism*
  • HeLa Cells
  • Humans
  • Mice, Inbred C57BL
  • Poly-ADP-Ribose Binding Proteins
  • Polyadenylation
  • Protein Biosynthesis
  • RNA Helicases
  • RNA Recognition Motif Proteins
  • RNA Stability
  • RNA, Messenger / metabolism*
  • Stress, Physiological

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • Poly-ADP-Ribose Binding Proteins
  • RNA Recognition Motif Proteins
  • RNA, Messenger
  • TDP-43 protein, human
  • DNA Helicases
  • G3BP1 protein, human
  • RNA Helicases