The FXR1 network acts as a signaling scaffold for actomyosin remodeling Journal Article


Authors: Chen, X.; Fansler, M. M.; Janjoš, U.; Ule, J.; Mayr, C.
Article Title: The FXR1 network acts as a signaling scaffold for actomyosin remodeling
Abstract: 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.
Keywords: gene; phosphorylation; rna-binding proteins; specificity; messenger-rna; domains; fragile-x-syndrome; nonmuscle myosin-ii; coiled-coil; contains
Journal Title: Cell
Volume: 187
Issue: 18
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2024-09-05
Start Page: 5048
End Page: 5063.e25
Language: English
ACCESSION: WOS:001309035900001
DOI: 10.1016/j.cell.2024.07.015
PROVIDER: wos
PMCID: PMC11380585
PUBMED: 39106863
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Christine Mayr -- Source: Wos
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MSK Authors
  1. Christine Mayr
    30 Mayr
  2. Xiuzhen Chen
    3 Chen