RNA-peptide interactions tune the ribozyme activity within coacervate microdroplet dispersions

Research output: Contribution to journal › Research article › Contributed › peer-review

Contributors

  • Basusree Ghosh - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Patrick M. McCall - , Clusters of Excellence PoL: Physics of Life, Chair of Spatiotemporal Organization of Subcellular Structures (PoL), Max Planck Institute of Molecular Cell Biology and Genetics, Max-Planck-Institute for the Physics of Complex Systems, Center for Systems Biology Dresden (CSBD), Leibniz Institute of Polymer Research Dresden (Author)
  • Kristian Kyle Le Vay - , Dortmund University of Technology (Author)
  • Archishman Ghosh - , Max Planck Institute of Molecular Cell Biology and Genetics, Max-Planck-Institute for the Physics of Complex Systems, Saarland University (Author)
  • Lars Hubatsch - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • David T. Gonzales - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Jan Brugués - , Clusters of Excellence PoL: Physics of Life, Chair of Spatiotemporal Organization of Subcellular Structures (PoL), Max Planck Institute of Molecular Cell Biology and Genetics, Max-Planck-Institute for the Physics of Complex Systems, Center for Systems Biology Dresden (CSBD) (Author)
  • Hannes Mutschler - , Dortmund University of Technology (Author)
  • T. Y. Dora Tang - , Max Planck Institute of Molecular Cell Biology and Genetics, Saarland University, Clusters of Excellence PoL: Physics of Life (Author)

Abstract

Membrane-free complex coacervate microdroplets are compelling models for primitive compartmentalisation with the ability to form from biological molecules. However, understanding how molecular interactions can influence physicochemical properties and catalytic activity of membrane-free compartments is still in its infancy. This is important for defining the function of membrane-free compartments during the origin of life as well as in modern biology. Here, we use RNA-peptide coacervate microdroplets prepared with prebiotically relevant amino acids and a minimal hammerhead ribozyme. This is a model system to probe the relationship between coacervate composition, its properties and ribozyme activity. We show that ribozyme catalytic activity is inhibited within the coacervate compared to buffer solution, whilst variations in peptide sequence can modulate rates and yield of the ribozyme within the coacervate droplet by up to 15-fold. The apparent ribozyme rate constant is anti-correlated with its concentration and correlated to its diffusion coefficient within the coacervates. Our results provide a relationship between the physicochemical properties of the coacervate microenvironment and the catalytic activity of the ribozyme where membrane-free compartments could provide a selection pressure to drive molecular evolution on prebiotic earth.

Details

Original languageEnglish
Article number8765
JournalNature communications
Volume16
Issue number1
Publication statusPublished - 1 Oct 2025
Peer-reviewedYes

External IDs

PubMed 41034201