G3BP1 ribonucleoprotein complexes regulate focal adhesion protein mobility and cell migration

Cell Rep. 2025 Feb 25;44(2):115237. doi: 10.1016/j.celrep.2025.115237. Epub 2025 Feb 1.

Abstract

The subcellular localization of mRNAs plays a pivotal role in biological processes, including cell migration. For instance, β-actin mRNA and its associated RNA-binding protein (RBP), ZBP1/IGF2BP1, are recruited to focal adhesions (FAs) to support localized β-actin synthesis, crucial for cell migration. However, whether other mRNAs and RBPs also localize at FAs remains unclear. Here, we identify hundreds of mRNAs that are enriched at FAs (FA-mRNAs). FA-mRNAs share characteristics with stress granule (SG) mRNAs and are found in ribonucleoprotein (RNP) complexes with the SG RBP. Mechanistically, G3BP1 binds to FA proteins in an RNA-dependent manner, and its RNA-binding and dimerization domains, essential for G3BP1 to form RNPs in SG, are required for FA localization and cell migration. We find that G3BP1 RNPs promote cell speed by enhancing FA protein mobility and FA size. These findings suggest a previously unappreciated role for G3BP1 RNPs in regulating FA function under non-stress conditions.

Keywords: CP: Cell biology; CP: Molecular biology; G3BP1; RNA localization; cell migration; focal adhesions; protein mobility; ribonucleoprotein complexes.

Publication types

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

MeSH terms

  • Animals
  • Cell Movement*
  • DNA Helicases* / metabolism
  • Focal Adhesions* / metabolism
  • Humans
  • Poly-ADP-Ribose Binding Proteins* / metabolism
  • Protein Binding
  • RNA Helicases* / metabolism
  • RNA Recognition Motif Proteins* / genetics
  • RNA Recognition Motif Proteins* / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism
  • Ribonucleoproteins* / metabolism
  • Stress Granules / metabolism

Substances

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

Associated data

  • GEO/GSE246956
  • GEO/GSE246955
  • GEO/GSE246499