Talk abstracts
Talk on Friday 02:15-02:30pm submitted by Tharun Selvam Mahendran
RNA-driven Percolation Transitions in Aging Biomolecular Condensates
Tharun Selvam Mahendran (Department of Biology, SUNY Buffalo), Gable M. Wadsworth (Department of Physics, SUNY Buffalo), Priya R. Banerjee (Department of Physics and Department of Biology, SUNY Buffalo)
Abstract:
Phase separation of protein and RNA complexes in living systems is driven by a complex interplay of homotypic and heterotypic interactions mediated by proteins, structured, and unstructured RNAs. We recently reported that RNAs are intrinsically poised to undergo an entropically-driven phase separation coupled to an enthalpically-driven percolation, where a system-spanning networking transition in the dense phase leads to their dynamical arrest and hysteretic phase behavior. Here, we investigate RNA-driven percolation transitions in the context of multicomponent protein-RNA condensates that closely mimic intracellular ribonucleoprotein (RNP) granules. We show that naturally occurring RNAs that form G-quadruplex structures drive an age-dependent liquid-to-solid transition of RNP condensates. Upon physical aging, the RNP condensate fluid network undergoes dramatic rearrangements and features a dynamically arrested viscoelastic solid core surrounded by a terminally viscous fluid shell. The timescale of the RNA-driven percolation transition of RNP condensates is tuned by the RNA chain length, valence, and mutations that modulate the stability of RNA G-quadruplex. Utilizing GC-rich RNAs that are associated with repeat expansion disorders, we further show that RNA-driven percolation transition universally engenders dynamical arrest of RNP condensates in a non-functional state. We posit that this aberrant age-dependent phase transition of RNA-protein condensates can be counteracted by factors and additives, such as ATP-dependent RNA binding proteins that can modulate RNA base pairing and base stacking interactions in the dense phase. The ability of RNA chaperones to alter an RNA’s phase separation and percolated network formation may provide a new lens to view their roles in modulating the physical aging of intracellular biomolecular condensates that are central to RNA biology.
References:
Wadsworth, G. M., Zahurancik, W. J., Zeng, X., Pullara, P., Lai, L. B., Sidharthan, V., Pappu, R. V., Gopalan, V., Banerjee, P. R.*, 2023. RNAs undergo phase transitions with lower critical solution temperatures. Nature Chemistry. In press. Manuscript available at bioRxiv. DOI: https://doi.org/10.1101/2022.10.17.512593.
Keywords: Phase separation coupled to percolation (PSCP), RNA G-quadruplex, RNP granules