In vivo reconstitution finds multivalent RNA-RNA interactions as drivers of meshlike condensates

Liquid-like condensates have been thought to be sphere-like. Recently, various condensates with filamentous morphology have been observed in cells. One such condensate is the TIS granule network that shares a large surface area with the rough endoplasmic reticulum and is important for membrane protein trafficking. It has been unclear how condensates with mesh-like shapes but dynamic protein components are formed. In vitro and in vivo reconstitution experiments revealed that the minimal components are a multivalent RNA-binding protein that concentrates RNAs that are able to form extensive intermolecular mRNA-mRNA interactions. mRNAs with large unstructured regions have a high propensity to form a pervasive intermolecular interaction network that acts as condensate skeleton. The underlying RNA matrix prevents full fusion of spherical liquid-like condensates, thus driving the formation of irregularly shaped membraneless organelles. The resulting large surface area may promote interactions at the condensate surface and at the interface with other organelles.

Automated summary

Liquid-like condensates in cells are not necessarily sphere-like, as various condensates with filamentous morphology have been observed. One example is the TIS granule network, which shares a large surface area with the rough endoplasmic reticulum and plays a crucial role in membrane protein trafficking. Reconstitution experiments have shown that a multivalent RNA-binding protein and RNAs with large unstructured regions can form a pervasive intermolecular interaction network that acts as a condensate skeleton.