James P. Saenz

Significance Lipids, which are essential for life and one of the most ancient biomolecules, can spontaneously self-assemble to form membranous bilayers, theoretically providing a surface that can serve to concentrate, protect, and regulate RNAs. Here, we show that direct RNA–lipid interactions can modulate ribozyme activity in a lipid-dependent manner. We further demonstrate that RNA–lipid binding is influenced by nucleotide content and base pairing of RNAs. This yields an essential framework for engineering RNA–lipid systems that can be regulated based on sequence specificity and introduces a mechanism for riboregulation in cellular, synthetic, and prebiotic systems.