RNA Controls PolyQ Protein Phase Transitions

Compartmentalization in cells is central to the spatial and temporal control of biochemistry. In addition to membrane-bound organelles, membrane-less compartments form partitions in cells. Increasing evidence suggests that these compartments assemble through liquid-liquid phase separation. However, the spatiotemporal control of their assembly, and how they maintain distinct functional and physical identities, is poorly understood. We have previously shown an RNA-binding protein with a polyQ-expansion called Whi3 is essential for the spatial patterning of cyclin and formin transcripts in cytosol. Here, we show that specific mRNAs that are known physiological targets of Whi3 drive phase separation. mRNA can alter the viscosity of droplets, their propensity to fuse, and the exchange rates of components with bulk solution. Different mRNAs impart distinct biophysical properties of droplets, indicating mRNA can bring individuality to assemblies. Our findings suggest that mRNAs can encode not only genetic information but also the biophysical properties of phase-separated compartments. [Display omitted] •RNA drives phase transition of Whi3, an RNA-binding protein with a long polyQ tract•RNA alters Whi3 droplet viscosity, dynamics, and their propensity to fuse•Different target mRNAs drive Whi3 to form droplets with distinct properties•Whi3 droplets mature and appear fibrillar over time Zhang et al. show that RNAs drive an RNA-binding protein with a polyQ expansion to undergo a phase transition to form dynamic droplets. RNA sequences influence droplet biophysical properties and may help keep aggregation-prone proteins in functional liquid-like states and avoid fibrous and potentially toxic aggregate states.