RNAs undergo phase transitions with lower critical solution temperatures

Wadsworth, G. M.; Zahurancik, W. J.; Zeng, X.; Pullara, P.; Lai, L. B.; Sidharthan, V.; Pappu, R. V.; Gopalan, V.; Banerjee, P. R.

doi:10.1101/2022.10.17.512593

bioRxiv · 10.1101/2022.10.17.512593

RNAs undergo phase transitions with lower critical solution temperatures

Wadsworth, G. M.·Zahurancik, W. J.·Zeng, X.·Pullara, P.·Lai, L. B.·Sidharthan, V.·Pappu, R. V.·Gopalan, V.·Banerjee, P. R.

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Abstract

Co-phase separation of RNAs and RNA-binding proteins is thought to drive the biogenesis of ribonucleoprotein granules. RNAs can also undergo phase transitions in the absence of proteins. However, the physicochemical driving forces of protein-free, RNA-driven phase transitions remain unclear. Here, we report that RNAs of various types undergo phase transitions with system-specific lower critical solution temperatures (LCSTs). This entropically-driven phase behavior requires Mg2+ ions and is an intrinsic feature of the phosphate backbone that is modulated by RNA bases. RNA-only condensates can additionally undergo enthalpically favorable percolation transitions within dense phases. This is enabled by a combination of Mg2+-dependent bridging interactions among phosphate groups and RNA base-stacking / base-pairing. Phase separation coupled to percolation can cause dynamical arrest of RNAs within condensates and can suppress the catalytic activity of an RNase P ribozyme. Our work highlights the need to incorporate RNA-driven phase transitions into models for RNP granule biogenesis.

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Wadsworth, G. M., Zahurancik, W. J., Zeng, X., Pullara, P., Lai, L. B., Sidharthan, V., Pappu, R. V., Gopalan, V., Banerjee, P. R.. 2022-10-18. RNAs undergo phase transitions with lower critical solution temperatures. https://doi.org/10.1101/2022.10.17.512593

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