A Multivalent RNA Matrix Drives Formation of Mesh-Like Condensates

Abstract

The TIS granule network is a constitutively expressed membraneless organelle that is important for trafficking of membrane proteins and is formed through assembly of the RNA-binding protein TIS11B. TIS granules have a mesh-like morphology that allows them to share a lot of surface area with the rough endoplasmic reticulum. It has been unclear how condensates with filamentous shapes, but dynamic protein components are formed. In vitro reconstitution of TIS granule-like condensates revealed that mRNAs with large unstructured regions, that are abundant in a subset of human 3′UTRs, are required for formation of mesh-like condensates. The unstructured regions allow formation of an extensive intermolecular mRNA-mRNA 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 promotes interactions at the condensate surface and at the interface with other organelles.