The FXR1 network acts as a signaling scaffold for actomyosin remodeling
- Cell. 2024 Sep 5;187(18):5048-5063.e25. doi: 10.1016/j.cell.2024.07.015.
- 1. Cancer Biology and Genetics Program, Sloan Kettering Institute, New York, NY 10065, USA.
- 2. National Institute of Chemistry, Hajdrihova 19, 1001 Ljubljana, Slovenia; Biosciences PhD Program, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.
- 3. National Institute of Chemistry, Hajdrihova 19, 1001 Ljubljana, Slovenia; UK Dementia Research Institute at King's College London, London SE5 9NU, UK.
- 4. Cancer Biology and Genetics Program, Sloan Kettering Institute, New York, NY 10065, USA. Electronic address: [email protected].
It is currently not known whether mRNAs fulfill structural roles in the cytoplasm. Here, we report the fragile X-related protein 1 (FXR1) network, an mRNA-protein (mRNP) network present throughout the cytoplasm, formed by FXR1-mediated packaging of exceptionally long mRNAs. These mRNAs serve as an underlying condensate scaffold and concentrate FXR1 molecules. The FXR1 network contains multiple protein binding sites and functions as a signaling scaffold for interacting proteins. We show that it is necessary for RhoA signaling-induced actomyosin reorganization to provide spatial proximity between kinases and their substrates. Point mutations in FXR1, found in its homolog FMR1, where they cause fragile X syndrome, disrupt the network. FXR1 network disruption prevents actomyosin remodeling-an essential and ubiquitous process for the regulation of cell shape, migration, and synaptic function. Our findings uncover a structural role for cytoplasmic mRNA and show how the FXR1 RNA-binding protein as part of the FXR1 network acts as an organizer of signaling reactions.