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Peer-reviewedCC BYNature chemical engineering

Genetic encoding and mutagenesis of RNA droplet phenotypes.

  • William Verstraeten1
  • Mai P Tran1
  • Alena Taskina1,2
  • Pranay Jaiswal3
  • Ivar S Haugerud3
  • Claudia Helbig1
  • Moritz Hamberger4,5,6,7
  • Edward W Green4,5,6
  • Michael Platten4,5,6,8,9,10
  • Christoph A Weber3
  • Kerstin Göpfrich1,2,10
10 affiliations
  1. 1Center for Molecular Biology of Heidelberg University (ZMBH), Heidelberg University, Heidelberg, Germany.
  2. 2Max Planck School Matter to Life, Heidelberg, Germany.
  3. 3Faculty of Mathematics, Natural Science, and Materials Engineering, Institute of Physics, University of Augsburg, Augsburg, Germany.
  4. 4German Cancer Research Center (DKFZ) Heidelberg, CCU Neuroimmunology and Brain Tumor Immunology, Heidelberg, Germany.
  5. 5German Cancer Consortium (DKTK), DKFZ, Core Center Heidelberg, Heidelberg, Germany.
  6. 6Department of Neurology, Medical Faculty Mannheim, MCTN, University of Heidelberg, Mannheim, Germany.
  7. 7Faculty of Bioscience, Heidelberg University, Heidelberg, Germany.
  8. 8Helmholtz Institute for Translational Oncology Mainz, Mainz, Germany.
  9. 9DKFZ-Hector Cancer Institute at the Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
  10. 10Cluster of Excellence SynthImmune, Heidelberg University, Heidelberg, Germany.
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Abstract

RNA droplets assembled from cotranscriptionally folded nanostructures have recently emerged as a promising platform for constructing protocells and minimal synthetic cell models. A custom-designed DNA template encodes an RNA nanostar that self-assembles into droplets by kissing-loop interactions. Here we show that such RNA droplets encapsulate their DNA template, creating a genotype-phenotype link. We find that low mutation rates in the DNA template increase the phenotypical and functional complexity of the RNA droplets. Surprisingly, mutagenesis leads to the formation of long-lived vacuoles. With theory and next-generation sequencing, we explain this emergent behavior. We identify mutant nanostars that facilitate the formation of vacuoles through altered interactions between nanostars. Strikingly, vacuolated droplets exhibit micrometer-scale movement driven by internal vacuole dynamics - an emergent function resulting from mutagenesis. Beyond motility, we show that the vacuoles can be used as subcompartments to store cargo in the RNA droplets. Our findings establish RNA droplets as self-contained, evolvable systems, opening new avenues for the bottom-up evolution of synthetic cells and origins-of-life research.

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Cite

BibTeXRIS
BibTeX
@article{verstraeten2026genetic,
  title = {{Genetic encoding and mutagenesis of RNA droplet phenotypes.}},
  author = {William Verstraeten and Mai P Tran and Alena Taskina and Pranay Jaiswal and Ivar S Haugerud and Claudia Helbig and Moritz Hamberger and Edward W Green and Michael Platten and Christoph A Weber and Kerstin Göpfrich},
  journal = {Nature chemical engineering},
  year = {2026},
  month = oct,
  doi = {10.1038/s44286-026-00454-4},
  url = {https://europepmc.org/article/MED/42903144},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Genetic encoding and mutagenesis of RNA droplet phenotypes.
AU  - William Verstraeten
AU  - Mai P Tran
AU  - Alena Taskina
AU  - Pranay Jaiswal
AU  - Ivar S Haugerud
AU  - Claudia Helbig
AU  - Moritz Hamberger
AU  - Edward W Green
AU  - Michael Platten
AU  - Christoph A Weber
AU  - Kerstin Göpfrich
PY  - 2026
DA  - 2026/10/07
JO  - Nature chemical engineering
DO  - 10.1038/s44286-026-00454-4
UR  - https://europepmc.org/article/MED/42903144
AB  - RNA droplets assembled from cotranscriptionally folded nanostructures have recently emerged as a promising platform for constructing protocells and minimal synthetic cell models. A custom-designed DNA template encodes an RNA nanostar that self-assembles into droplets by kissing-loop interactions. Here we show that such RNA droplets encapsulate their DNA template, creating a genotype-phenotype link. We find that low mutation rates in the DNA template increase the phenotypical and functional complexity of the RNA droplets. Surprisingly, mutagenesis leads to the formation of long-lived vacuoles. With theory and next-generation sequencing, we explain this emergent behavior. We identify mutant nanostars that facilitate the formation of vacuoles through altered interactions between nanostars. Strikingly, vacuolated droplets exhibit micrometer-scale movement driven by internal vacuole dynamics - an emergent function resulting from mutagenesis. Beyond motility, we show that the vacuoles can be used as subcompartments to store cargo in the RNA droplets. Our findings establish RNA droplets as self-contained, evolvable systems, opening new avenues for the bottom-up evolution of synthetic cells and origins-of-life research.
SN  - 2948-1198
ER  -