Abstract

Membraneless organelles like stress granules are active liquid-liquid phase-separated droplets that are involved in many intracellular processes. Their active and dynamic behavior is often regulated by ATP-dependent reactions. However, how exactly membraneless organelles control their dynamic composition remains poorly understood. Herein, we present a model for membraneless organelles based on RNA-containing active coacervate droplets regulated by a fuel-driven reaction cycle. These droplets emerge when fuel is present, but decay without. Moreover, we find these droplets can transiently up-concentrate functional RNA which remains in its active folded state inside the droplets. Finally, we show that in their pathway towards decay, these droplets break apart in multiple droplet fragments. Emergence, decay, rapid exchange of building blocks, and functionality are all hallmarks of membrane-less organelles, and we believe that our work could be powerful as a model to study such organelles.

Highlights

  • Membraneless organelles like stress granules are active liquid-liquid phase-separated droplets that are involved in many intracellular processes

  • Recent work has demonstrated that some of these organelles are actively regulated by ATP-dependent chemical reaction cycles.[7,9,10]

  • These findings suggest that some of the membraneless organelles are active droplets, i.e., these droplets exist out of equilibrium and are regulated by chemical reactions

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Summary

Introduction

Membraneless organelles like stress granules are active liquid-liquid phase-separated droplets that are involved in many intracellular processes. Control experiments confirmed that the transient droplet formation was a result of fuel, RNA, and peptide combined (see Supplementary Fig. 4).

Results
Conclusion
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