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.

Cholesterol renders mammalian cell membranes more compact by reducing the amount of voids in the membrane structure. Because of this, cholesterol is known to regulate the ability of cell membranes to prevent the permeation of water and water-soluble molecules through the membranes. Meanwhile, it is also known that even seemingly tiny modifications in the chemical structure of cholesterol can lead to notable changes in membrane properties. The question is, how significantly do these small changes in cholesterol structure affect the permeability barrier function of cell membranes? In this work, we applied fluorescence methods as well as atomistic molecular dynamics simulations to characterize changes in lipid membrane permeability induced by cholesterol oxidation. The studied 7β-hydroxycholesterol (7β-OH-chol) and 27-hydroxycholesterol (27-OH-chol) represent two distinct groups of oxysterols, namely, ring- and tail-oxidized cholesterols, respectively. Our previous research showed that the oxidation of the cholesterol tail has only a marginal effect on the structure of a lipid bilayer; however, oxidation was found to disturb membrane dynamics by introducing a mechanism that allows sterol molecules to move rapidly back and forth across the membrane—bobbing. Herein, we show that bobbing of 27-OH-chol accelerates fluorescence quenching of NBD-lipid probes in the inner leaflet of liposomes by dithionite added to the liposomal suspension. Systematic experiments using fluorescence quenching spectroscopy and microscopy led to the conclusion that the presence of 27-OH-chol increases membrane permeability to the dithionite anion. Atomistic molecular dynamics simulations demonstrated that 27-OH-chol also facilitates water transport across the membrane. The results support the view that oxysterol bobbing gives rise to successive perturbations to the hydrophobic core of the membrane, and these perturbations promote the permeation of water and small water-soluble molecules through a lipid bilayer. The observed impairment of permeability can have important consequences for eukaryotic organisms. The effects described for 27-OH-chol were not observed for 7β-OH-chol which represents ring-oxidized sterols.

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. Here we show that lipid membranes can act as RNA organization platforms, introducing a novel mechanism for ribo-regulation. The activity of R3C ribozyme can be modified by the presence of lipid membranes, with RNA-lipid interactions dependent on RNA sequence, structure 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 artifially modifying the R3C-substrate sequence to enhance membrane binding we unexpectedly generated a lipid sensitive riboswitch. These findings introduce RNA-lipid interactions as a tool for developing riboswitches and novel RNA-based lipid biosensors, and bear significant implications for RNA World scenarios for the origin of life.

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Abstract. Architectural acoustics of contemporary sacred buildings is still an under-appreciated issue. Many contemporary churches are not functional enough due to acoustic defects which occur there. The study discusses issues of the modern Catholic church, where acoustic problems surface as high reverberant noise levels. The building under investigation, i.e. the Church of the Visitation of the Blessed Virgin Mary, is the biggest contemporary church in Poznań, Poland, as its internal volume amounts to 16,800 m³. On the basis of in situ investigations, a computer model of the church was built and a series of simulations were carried out to determine correct treatment in order to achieve satisfactory acoustic conditions. The main assumption was to find such a solution as not to affect the modernist architecture of the church.