Universal Cold RNA Phase Transitions
Paolo Rissone, Aurelien Severino, Isabel Pastor, Felix Ritort
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RNA's diversity of structures and functions impacts all life forms since primordia. We use calorimetric force spectroscopy to investigate RNA folding landscapes in previously unexplored low-temperature conditions. We find that Watson-Crick RNA hairpins, the most basic secondary structure elements, undergo a glass-like transition below T_G 20 ^C where the heat capacity abruptly changes and the RNA folds into a diversity of misfolded structures. We hypothesize that an altered RNA biochemistry, determined by sequence-independent ribose-water interactions, outweighs sequence-dependent base pairing. The ubiquitous ribose-water interactions lead to universal RNA phase transitions below T_G, such as maximum stability at T_S 5 ^C where water density is maximum, and cold denaturation at T_C-50^C. RNA cold biochemistry may have a profound impact on RNA function and evolution.