Abstract
RNA is a ubiquitous biomolecule that can serve as both catalyst and information carrier. Understanding how RNA bioactivity is controlled is crucial for elucidating its physiological roles and potential applications in synthetic biology. Here, we show that lipid membranes can act as RNA organization platforms, introducing a mechanism for riboregulation. The activity of R3C ribozyme can be modified by the presence of lipid membranes, with direct RNA-lipid interactions dependent on RNA nucleotide content, base pairing, and length. In particular, the presence of guanine in short RNAs is crucial for RNA-lipid interactions, and G-quadruplex formation further promotes lipid binding. Lastly, by artificially modifying the R3C substrate sequence to enhance membrane binding, we generated a lipid-sensitive ribozyme reaction with riboswitch-like behavior. These findings introduce RNA-lipid interactions as a tool for developing synthetic riboswitches and RNA-based lipid biosensors and bear significant implications for RNA world scenarios for the origin of life.
Highlights
R NA performs diverse functions, ranging from information storage to regulation of other biomolecules and direct catalysis of biochemical reactions
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
Summary
R NA performs diverse functions, ranging from information storage to regulation of other biomolecules and direct catalysis of biochemical reactions. For both synthetic biology and understanding the origin of self-replicating organisms, RNA has intrinsic appeal: It can serve the functions of both DNA (information storage) and proteins (enzymes), obviating the need for translation machineries and protein chaperones. Localization to a lipid surface brings RNA into a physicochemically unique microenvironment with sharp gradients of hydrophobicity, electrical permittivity, and water activity Through these effects, RNA–lipid interactions could provide a powerful mechanism for modulating RNA activity. 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. 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
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