Effects of lipid membranes on RNA catalytic activity and stability

Abstract

RNA plays crucial roles in cellular organization and metabolism, and modulating its activity is essential for maintaining cellular functions. RNA activity, involving both catalytic (ribozymes) and translation processes, is controlled via myriad mechanisms involving different binding partners such as proteins and smaller polar solutes. We previously reported that lipid membranes can directly interact with the artificial R3C ribozyme changing its activity, however the effect of lipids on naturally occurring ribozymes remains unknown. Here, we report that both catalytic activity as well as RNA integrity can be controlled by the presence of different lipid membranes. Gel-phase lipid membranes decreased the activity of hepatitis delta virus (HDV) ribozyme and increased the activity of a hammerhead (HH) ribozyme. The presence of lipid liquid membrane surfaces triggered RNA degradation with greater degradation occurring in the single-stranded regions of RNA. The interplay between RNA activity and stability in the presence of different lipid membranes introduces multiple possibilities, where different combinations of ribozyme and lipid membrane composition could produce different effects on activity. Taken together, these observations support the hypothesis that the activity of both natural and artificial RNAs can be modulated by lipid membranes which, in turn, provides a foundation for the development of novel riboswitch-like molecules, and lipid membrane-based RNA-biosensors.