Lipid membranes modulate the activity of RNA through sequence-dependent interactions

Research output: Contribution to journalResearch articleContributedpeer-review

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 RNAbased lipid biosensors and bear significant implications for RNA world scenarios for the origin of life.

Details

Original languageEnglish
Article numbere2119235119
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America : PNAS
Volume119
Issue number4
Publication statusPublished - 18 Jan 2022
Peer-reviewedYes

External IDs

Scopus 85123101242
unpaywall 10.1073/pnas.2119235119
PubMed 35042820
WOS 000758464700003
Mendeley c45f8e71-a129-3a1e-9ac3-595ea0c5ffb0

Keywords

ASJC Scopus subject areas

Keywords

  • Lipids, RNA, RNA world, Ribozymes, Base Sequence/genetics, Riboswitch/genetics, Binding Sites/genetics, RNA/chemistry, RNA, Catalytic/chemistry, Base Pairing/genetics, Cell Membrane/metabolism, Genetic Engineering/methods, Lipid Metabolism/physiology, Lipids/genetics, Nucleic Acid Conformation, Membrane Lipids/metabolism

Library keywords