Cellular RNA concentrations regulate RNA-RBP condensate dynamics

Abstract

Compartmentalization plays a crucial role in orchestrating complex biochemical reactions within cells through the presence of both large membrane-bound organelles and smaller, dynamic nucleic acid-protein condensates. In higher eukaryotic cells, numerous RNA-binding proteins possess extensive disordered domains, rendering them susceptible to phase separation on interaction with RNA and forming dynamic liquid-like condensates. Many of these RBPs aggregate in ageing-associated neurodegenerative conditions like ALS and FTD. Our previous work has demonstrated that high nuclear RNA concentration keep aggregation prone RBPs in soluble state. Our studies have shown that global RNA metabolism in neurodegeneration and ageing conditions control the phase behavior and properties of the RNA-RBP condensates mainly stress granules.