RNA stability is critically influenced by the ionic environment, yet the sequence-dependent rules governing ion effects remain unclear. Here, we combined single-molecule optical tweezers with all-atom molecular dynamics simulations to study a G:U-rich hairpin derived from the long noncoding RNA MALAT1. Optical tweezers experiments revealed that potassium stabilizes this hairpin more effectively than sodium, inverting the conventional hierarchy of monovalent ion effects. Simulations showed that this enhanced stability arises from tighter compaction in the presence of potassium and preferential localization of K + near G:U wobble-rich regions. In contrast, sodium interacts less specifically, providing weaker stabilization. The addition of magnesium further increased hairpin stability in both Na + and K + environments, highlighting cooperative effects between monovalent and divalent ions. These findings reveal new unique ion-dependent characteristic of G:U wobble base with broad implication in function of structural switches and ribosome dynamics.
Ouzon et al. (Sun,) studied this question.
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