Review toward all RNA structures, concisely

Profound insights regarding nucleic acid structure and function can be gleaned from very simple, direct, and chemistry-based strategies. Our approach strives to incorporate the elegant physical insights that Don Crothers instilled in those who trained in his laboratory. Don emphasized the advantages of focusing on direct and concise experiments even when the final objective was to understand something complex-potentially including the large-scale architectures of the genomes of RNA viruses and the transcriptomes of cells. Here, the author reviews the intellectual path, and a few detours, that led to the development of the SHAPE-MaP and RING-MaP technologies for interrogating RNA structure and function at large scales. The author also argues that greater attention to creating direct, less inferential experiments will convert "omics" investigations into lasting and definitive contributions to our understanding of biological function.