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Born to Condense: Polysomes Drive Cotranslational Condensation of Biomolecular Condensate Proteins

Zhouyi He (贺周易)*

Chi Fung Willis Chow† and Agnes Toth-Petroczy‡

Jens-Uwe Sommer§

Tyler S. Harmon∥

  • *Contact author: he@ipfdd.de
  • †Contact author: chow@mpi-cbg.de
  • ‡Contact author: tothpet@mpi-cbg.de
  • §Contact author: sommer@ipfdd.de
  • ∥Contact author: tylerharmon@ipfdd.de
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PRX Life 4, 043008 – Published 30 October, 2026

DOI: https://doi.org/10.1103/gjtk-ddjr

Abstract

Biomolecular condensates formed by liquid-liquid phase separation organize many cellular processes, yet it remains unclear how condensate localization is coupled to protein synthesis. In particular, proteins are often translated on polysomes, where multiple ribosomes on a single mRNA generate a bottlebrush-like assembly of nascent chains, raising the possibility that translation itself could be spatially coupled to condensates. Here we develop a theoretical framework for CoTranslational Condensation (CTC), in which nascent chains on a polysome for condensate proteins interact with their condensate and thus localize translation there. Using coarse-grained simulations, we show that protein domain architecture dictates the thermodynamics of CTC, consistent with a Langmuir adsorption model. Proteins with high-affinity regions exposed early on nascent chains display much stronger condensate association than architectures in which these regions appear only late in translation. A bioinformatic analysis of 7667 condensate-associated proteins further shows that sequence architectures compatible with strong CTC are common. At the dynamical level, combining simulations with reaction-diffusion modeling reveals that CTC is kinetically feasible within typical polysome lifetimes, either through densely packed polysomes nucleating new condensates or via diffusion to preexisting condensates. As an illustrative consequence, we show that CTC can reduce the accumulation of unmodified protein intermediates by localizing their synthesis with condensates, where modification can occur promptly. Together, our results establish physical principles for how translation can couple to phase separation and identify protein architectures and cellular regimes that favor CTC.

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This article appears in the following collection:

Collection on Physics of Biomolecular Condensates

From the fundamentals of phase separation, dynamics and structure of condensates in biological settings, to advanced imaging methods, this special collection presented by PRX Life showcases exciting and timely work on the physics of biomolecular condensates.

This Invited Collection is coordinated by PRX Life Associate Editor Christoph Weber, in consultation with Jerelle Joseph, Simon Alberti, and Tanja Mittag. Every article published in this collection underwent a rigorous peer review process, adhering to the same high standards applied to all papers handled by the journal. The PRX Life editorial team managed the peer review and made all editorial decisions.

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PRX Life 4, 043008– Published 30 October, 2026
  • Received 31 March 2026
  • Accepted 8 September 2026
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