G3BP1 promotes intermolecular RNA-RNA interactions during RNA condensation

Abstract

Ribonucleoprotein (RNP) granules are biomolecular condensates requiring RNA and proteins to assemble. Stress granules are RNP granules formed upon increases in non-translating messenger ribonucleoprotein particles (mRNPs) during stress. G3BP1 and G3BP2 proteins are proposed to assemble stress granules through multivalent crosslinking of RNPs. We demonstrate that G3BP1 also has “condensate chaperone” functions, which promote the assembly of stress granules but are dispensable following initial condensation. Following granule formation, G3BP1 is dispensable for the RNA component of granules to persist in vitro and in cells when RNA decondensers are inactivated. These results demonstrate that G3BP1 functions as an “RNA condenser,” a protein that promotes intermolecular RNA-RNA interactions stabilizing RNA condensates, leading to RNP granule persistence. Moreover, the stability of RNA-only granules highlights the need for active mechanisms limiting RNP condensate stability and lifetime. • G3BP1 promotes the formation of intermolecular RNA-RNA interactions in vitro • Base-pairing interactions contribute to RNA-RNA interaction stability • Stress granules and nucleolar RNAs persist in assemblies without protein scaffolds • G3BP1 can act as a condensate chaperone Parker et al. demonstrate that some proteins responsible for organizing ribonucleoprotein granules can chaperone intermolecular RNA-RNA interactions in addition to their role in scaffolding. These findings cement RNA-RNA interaction networks as a key component of granules, highlighting the need to further explore the regulation of RNA dynamics within granules.

Topics & Concepts