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*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

6 Citations (Scopus)


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
Early online date6 Nov 2023
Publication statusPublished - Dec 2023

Scopus Subject Areas

  • Chemistry(all)
  • Chemical Engineering(all)


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