Major Groove Accessibility of RNA

Chemical acylation experiments showed that the RNA major groove, often assumed to be too deep and narrow to permit recognition interactions, is accessible at duplex termini. Reactivity extended further into the helix in the 5' than in the 3' direction. Asymmetric and large loops between helices uncoupled them, which yielded both enhanced reactivity at terminal base pairs and weaker stabilization enthalpy compared to that in small loops or symmetric loops of the same size. Uncoupled helices have effective helix ends with accessible major grooves; such motifs are attractive contributors to protein recognition, tertiary folding, and catalysis.