RNAs are essential components of biological pathways that result in human disease making them attractive therapeutic targets. Currently, NMR spectroscopy is the only high-resolution technique capable of probing RNA interactions in solution. Although NMR spectroscopy is well-suited to characterize macromolecular interactions at atomic-level detail, the currently available isotopic labeling strategies and NMR methodologies are limited to relatively small RNAs (~ 30 nts, ~ 10 kDa). This size limitation is due to poor sensitivity and limited spectral resolution both of which worsen with increasing size. Here I present novel isotopic labeling schemes and NMR experiments to help expand the size limitations of NMR. These new technologies are then applied to characterize the structure and dynamics of a non-coding RNA from Kaposi’s sarcoma-associated herpesvirus (KSHV) that causes cancer in AIDS patients.