RNA: Tools for Cell Biology

National Heart, Lung, And Blood Institute

Investigators

Linked publications, trials & patents

Abstract

This year we reported the structural basis of function of a novel fluorogenic RNA aptamer called Beetroot. This RNA functions as a dimer, and is over 70% sequence-identical to another, previously characterized fluorescence turn-on aptamer called Corn. Corn is a homodimer that binds one molecule of fluorophore at its dimerization interface. Completely unexpected, the co-crystal structure of Beetroot revealed that its dimerization interface does not bind fluorophore. Instead, each protomer has evolved a fluorophore binding site that is distant from the dimerization interface, such that the two fluorophores bound to the dimeric RNA are separated by 30 . Biophysical characterization demonstrates electronic coupling between the two sites. Structure-based molecular engineering succeeded in generating a heterodimeric variant of Beetroot, in which the two binding sites have different fluorophore preferences. Further engineering of such heterodimeric RNAs will open new possibilities in the field of synthetic biology, as they would enable the use of FRET to monitor RNA dimerization.