Understanding the molecular recognition underlying RNA-ligand complex formation is of key importance to explain RNA regulatory function of riboswitches and to support the development of low molecular weight RNA binders as starting points for RNA-targeting drugs. Here, we report magic-angle spinning solid-state NMR spectroscopic studies enhanced by dynamic nuclear polarization (MAS-DNP) to determine the molecular recognition of a ligand-RNA riboswitch complex. We benchmarked different labeling strategies for four large RNAs (70-86 nt) of the aptamer domain of a 2’deoxyguanosine-sensing riboswitch from Mesoplasma florum. Samples were either prepared by chemo-enzymatic approaches or by solid-phase chemical RNA synthesis employing different labeling schemes of riboswitches of up to 86 nucleotides. RNA-ligand complexes were prepared by addition of their cognate metabolite. We show that nucleotide- and ligand-selective labeling are a prerequisite for the MAS-DNP studies to reduce the NMR signal overlap present in such large RNAs. We further extend site-specific labeling to atom-specific labeling that allowed us to derive the structure of the ligand binding pocket extending the application of 2D-13C,15N-TEDOR experiments. The work described here opens the avenue for the investigation of large RNA-ligand complexes by MAS-DNP.