A mechanism for MEX-5-driven disassembly of PGL-3/RNA condensates in vitro

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Natasha S. Lewis - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Silja Zedlitz - , Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck School Matter to Life (Autor:in)
  • Hannes Ausserwöger - , University of Cambridge (Autor:in)
  • Patrick M. McCall - , Exzellenzcluster PoL: Physik des Lebens, Professur für die Organisation Subzelluärer Strukturen in Raum und Zeit (PoL), Max Planck Institute of Molecular Cell Biology and Genetics, Zentrum für Systembiologie Dresden (CSBD), Leibniz-Institut für Polymerforschung Dresden, Max-Planck-Institut für Physik komplexer Systeme (Autor:in)
  • Lars Hubatsch - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Marco Nousch - , Martin-Luther-Universität Halle-Wittenberg (Autor:in)
  • Martine Ruer-Gruß - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Carsten Hoege - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Frank Jülicher - , Max-Planck-Institut für Physik komplexer Systeme (Autor:in)
  • Christian R. Eckmann - , Martin-Luther-Universität Halle-Wittenberg (Autor:in)
  • Tuomas P.J. Knowles - , University of Cambridge (Autor:in)
  • Anthony A. Hyman - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)

Abstract

MEX-5 regulates the formation and dissolution of P granules in Caenorhabditis elegans embryos, yet the thermodynamic basis of its activity remains unclear. Here, using a time-resolved in vitro reconstitution system, we show that MEX-5 dissolves preassembled liquid-like PGL-3/RNA condensates by altering RNA availability and shifting the phase boundary. We develop a microfluidic assay to systematically analyze how MEX-5 influences phase separation. By measuring the contribution of PGL-3 to phase separation, we show that MEX-5 reduces the free energy of PGL-3, shifting the equilibrium toward dissolution. Our findings provide a quantitative framework for understanding how RNA-binding proteins modulate condensate stability and demonstrate the power of microfluidics in precisely mapping phase transitions.

Details

OriginalspracheEnglisch
Aufsatznummere2412218122
FachzeitschriftProceedings of the National Academy of Sciences of the United States of America
Jahrgang122
Ausgabenummer20
PublikationsstatusVeröffentlicht - 20 Mai 2025
Peer-Review-StatusJa

Externe IDs

PubMed 40354522

Schlagworte

ASJC Scopus Sachgebiete

Schlagwörter

  • C. elegans, phase-separation, polarity