Dr. James P. Sáenz, TU Dresden

RNA is a ubiquitous biomolecule that can serve as both catalyst and information carrier. Understanding how RNA activity is controlled and how it in turn regulates bioactivity is crucial for elucidating its physiological roles and potential applications in synthetic biology. We demonstrate how lipid membranes can act as RNA organization platforms, introducing a novel mechanism for ribo-regulation. The activity of the 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, while double-stranded RNAs further increase lipid-binding affinity. Lastly, by artificially modifying the R3C substrate sequence to enhance membrane binding we generated a lipid-sensitive R3C substrate with riboswitch-like behavior. These findings introduce RNA-lipid interactions as a tool for developing synthetic riboswitches and novel RNA-based lipid biosensors, and bear significant implications for RNA World scenarios for the origin of life.

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