3-DIMENSIONAL HETERONUCLEAR NMR-STUDIES OF RNA

MULTIDIMENSIONAL heteronuclear NMR has revolutionized solution structure determinations of proteins 1-3. But this technique has not been applied to nucleic acids because of difficulties in the synthesis of isotopically (C-13 and/or N-15) labeLled molecules. Here we report the application of three-dimensional heteronuclear NMR to the study of a uniformly C-13/N-15 or N-15-labelled RNA duplex of defined sequence. These experiments simplify resonance assignment and the analysis of proton-proton nuclear Overhauser effects 4 (and therefore distance information) in the molecule. Our results show that it is now possible to determine the structures of larger and more complex RNAs using multidimensional heteronuclear NMR.