mRNA-Scaffolded Cytoplasmic Compartments

The cytoplasm of vertebrate cells is compartmentalized into the cytosol and several messenger RNA (mRNA)-scaffolded condensates, present at steady-state conditions and in the absence of stress. They include TIS granules and the FXR1 network and act as translation, folding, and signaling environments. Therefore, in addition to serving as templates for protein synthesis, mRNAs play essential roles in cytoplasmic organization. However, not all mRNAs function as condensate scaffolds. Whereas mRNAs with short and structured 3' untranslated regions (UTRs) usually diffuse freely and localize to the cytosol, scaffold mRNAs are characterized by long and multivalent 3' UTRs. Scaffold mRNAs are responsible for the characteristic irregular, network-like morphology of mesh-like condensates and play active, functional roles during protein biosynthesis. For example, mesh-like condensates act as folding environments for proteins with long intrinsically disordered regions, where multivalent 3' UTRs act as cotranslational chaperones to prevent protein misfolding. The scaffold function of mRNAs is also important for post-translational processes, where the mRNA-mediated proximity of signaling factors promotes cellular signaling reactions. In this review, the discovery of cytoplasmic mRNA-scaffolded mesh-like compartments and their currently known assembly principles and biological roles are discussed.