Dresden International Graduate School for Interdisciplinary Life Sciences

Tomasz Czerniak, from James Sáenz Group, will defend his PhD thesis
Mechanism and functional application of RNA-lipid interactions for riboregulation

Abstract

RNA is a ubiquitous biomolecule that can serve as both a catalyst and an information carrier. Understanding how RNA bioactivity is controlled is crucial for elucidating its physiological roles and potential applications in synthetic biology. Here, I show that lipid membranes can act as RNA organization platforms, introducing a mechanism for riboregulation. The ribozyme activity 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 the formation of base-paired RNA structures further promotes lipid binding. By artificially modifying the R3C substrate sequence to enhance membrane binding, I generated a lipid-sensitive ribozyme reaction with riboswitch-like behaviour. Lipid liquid membranes bind RNA species with high sequence and structure specificity, which might trigger RNA-self cleavage events. Preliminary data suggests that lipid membranes might have influence on the RNA folding and structure stability. Taken together, 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.