%0 Journal Article
%T Universal cold RNA phase transitions.
%A Rissone P
%A Severino A
%A Pastor I
%A Ritort F
%J Proc Natl Acad Sci U S A
%V 121
%N 34
%D 2024 Aug 20
%M 39150781
%F 12.779
%R 10.1073/pnas.2408313121
%X 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 [Formula: see text]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 TG, such as maximum stability at [Formula: see text]C where water density is maximum, and cold denaturation at [Formula: see text]C. RNA cold biochemistry may have a profound impact on RNA function and evolution.