The FXR1 network acts as a signaling scaffold for actomyosin remodeling.

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. [Display omitted] • Long mRNAs and bound FXR1 act as scaffolds of a dynamic cytoplasmic mRNP network • Most of FXR1 is recruited into the network by its multiple protein binding sites • Signaling molecules with multiple weak binding sites for FXR1 are also recruited • The FXR1 network enables signaling reactions by providing proximity between reactants Exceptionally long mRNAs are bound by the RNA-binding protein FXR1 and generate a cytoplasmic mRNA protein condensate network. The long mRNAs have structural roles as scaffolds of the FXR1 network, which enables signaling reactions by providing proximity between reactants. [ABSTRACT FROM AUTHOR]