FMRP modulates stress granule remodelling in cancer cells via G3BP1

Abstract

Stress granules (SGs) are dynamic, phase-dense cytosolic particles assembled through weak protein-RNA interactions. They form in response to cellular stress and play important roles in mRNA metabolism, translational control and cell survival. Fragile X Messenger Ribonucleoprotein 1 (FMRP), a multifunctional RNA-binding protein mutated or absent in Fragile X Syndrome, has recently emerged as a relevant factor in SG organization in cholangiocarcinoma and melanoma cells exposed to oxidative stress induced by sodium arsenite. We show that FMRP co-localizes with the SG marker G3BP1 and contributes to the maintenance of its protein levels and cytoplasmic distribution under stress conditions. FMRP depletion leads to a marked reduction in G3BP1 expression and mRNA abundance, altered SG assembly competence, and increased cellular sensitivity to stress. Furthermore, FMRP associates with other SG components, including TIA-1, and modulates the organization of SGs without affecting TIA-1 expression. Overall, our findings support a role for FMRP as a regulator of SG dynamics and identify the FMRP–G3BP1 axis as a candidate pathway for further investigation in aggressive and treatment-resistant cancers and in tumor adaptation to oxidative stress across distinct cellular contexts and survival programs.