Novel Conformation of an RNA Structural Switch

[Image: see text] The RNA duplex, (5′GACGAGUGUCA)(2), has two conformations in equilibrium. The nuclear magnetic resonance solution structure reveals that the major conformation of the loop, 5′GAGU/3′UGAG, is novel and contains two unusual Watson–Crick/Hoogsteen GG pairs with G residues in the syn conformation, two A residues stacked on each other in the center of the helix with inverted sugars, and two bulged-out U residues. The structure provides a benchmark for testing approaches for predicting local RNA structure and a sequence that allows the design of a unique arrangement of functional groups and/or a conformational switch into nucleic acids.