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Authors
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Lewis, N. S.; Zedlitz, S.; Ausserwöger, H.; McCall, P. M.; Hubatsch, L.; Nousch, M.; Ruer-Gruß, M.; Hoege, C.; Jülicher, F.; Eckmann, C. R.; Knowles, T. P. J.; Hyman, A. A.
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Title
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A mechanism for MEX-5-driven disassembly of PGL-3/RNA condensates in vitro
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Date
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12.05.2025
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Number
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0
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Abstract
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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.
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Publisher
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National Academy of Sciences
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Wikidata
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Citation
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Proceedings of the National Academy of Sciences of the United States of America (PNAS) 122 (2025) e2412218122
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DOI
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https://www.pnas.org/doi/10.1073/pnas.2412218122
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Tags
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