RNAs undergo phase transitions with lower critical solution temperatures

Gable M. Wadsworth, Walter J. Zahurancik, Xiangze Zeng, Paul Pullara, Lien B. Lai, Vaishnavi Sidharthan, Rohit V. Pappu, Venkat Gopalan, Priya R. Banerjee

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Co-phase separation of RNAs and RNA-binding proteins drives 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 various types of RNA undergo phase separation with system-specific lower critical solution temperatures. This entropically driven phase separation is an intrinsic feature of the phosphate backbone that requires Mg2+ ions and is modulated by RNA bases. RNA-only condensates can additionally undergo enthalpically favourable percolation transitions within dense phases. This is enabled by a combination of Mg2+-dependent bridging interactions between phosphate groups and RNA-specific base stacking and base pairing. Phase separation coupled to percolation can cause dynamic arrest of RNAs within condensates and suppress the catalytic activity of an RNase P ribozyme. Our work highlights the need to incorporate RNA-driven phase transitions into models for ribonucleoprotein granule biogenesis. [Figure not available: see fulltext.].

Original languageEnglish
Pages (from-to)1693-1704
Number of pages12
JournalNature Chemistry
Issue number12
StatePublished - Dec 2023


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