High-throughput dissection of the thermodynamic and conformational properties of a ubiquitous class of RNA tertiary contact motifs

Significance We would like to have a predictive understanding of how RNAs form and interconvert between intricate three-dimensional shapes that are essential to function. Despite great structural diversity, RNAs are built from a limited set of structural motifs so that a predictive model may arise from the in-depth understanding of these building blocks. We used a quantitative, high-throughput approach to investigate the thermodynamic and conformational properties of the tetraloop/tetraloop receptor (TL/TLR), a ubiquitous RNA tertiary contact motif. Our investigation of 1,493 TLRs and two TLs revealed classes of TL/TLR thermodynamic behavior. One class displayed conserved conformation across sequences and appears to be thermodynamically selected in biology. Other classes are conformationally diverse and may be selected for flexibility instead of stability.