RNA: Tools for Cell Biology

National Heart, Lung, And Blood Institute

Investigators

Linked publications, trials & patents

Abstract

Our collaborators in the Jaffrey laboratory at Cornell and in the Unrau laboratory at Simon Fraser had previously reported the development of the fluorescent RNA modules called 'Spinach' and 'RNA Mango', rsepectively, but further improvement was hampered by a complete lack of knowledge of its structural and biophysical basis of function. In 2014, we determined the structure of Spinach, revealing an unprecedented mode of RNA-fluorophore interaction, which relies on a G-quadruplex motif. In 2016-2017, we determined the crystal structure of RNA Mango, and disocovered that this fluorogenic RNA binds its chromophore between a three-tiered G-quadruplex and three flap nucleotides. Consistent with the modest quantum yield of the RNA-dye complex, the two heterocycles of the latter are not in plane. Since a planar arrangement is predicted to maximize quantum yield (indeed, in Spinach, which has a quantum yield of over 0.7, the dye heterocyles are planar) this immediately suggests avenues for further improving the fluorescence properties of RNA Mango.