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 $\mathbf{ T_G\sim 20 ^{ \circ}}$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 $\mathbf{ T_G}$, such as maximum stability at $\mathbf{ T_S\sim 5 ^{ \circ}}$C where water density is maximum, and cold denaturation at $\mathbf{ T_C\sim-50^{ \circ}}$C. RNA cold biochemistry may have a profound impact on RNA function and evolution.
Categories: q-bio.BM physics.bio-ph q-bio.QM stat.ME
