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Dynamical control enables the formation of demixed biomolecular condensates

Author

Listed:
  • Andrew Z. Lin

    (Washington University in St. Louis)

  • Kiersten M. Ruff

    (Washington University in St. Louis)

  • Furqan Dar

    (Washington University in St. Louis)

  • Ameya Jalihal

    (Duke University)

  • Matthew R. King

    (Washington University in St. Louis)

  • Jared M. Lalmansingh

    (Washington University in St. Louis)

  • Ammon E. Posey

    (Washington University in St. Louis)

  • Nadia A. Erkamp

    (Washington University in St. Louis
    University of Cambridge, Lensfield Road)

  • Ian Seim

    (Duke University)

  • Amy S. Gladfelter

    (Duke University)

  • Rohit V. Pappu

    (Washington University in St. Louis)

Abstract

Cellular matter can be organized into compositionally distinct biomolecular condensates. For example, in Ashbya gossypii, the RNA-binding protein Whi3 forms distinct condensates with different RNA molecules. Using criteria derived from a physical framework for explaining how compositionally distinct condensates can form spontaneously via thermodynamic considerations, we find that condensates in vitro form mainly via heterotypic interactions in binary mixtures of Whi3 and RNA. However, within these condensates, RNA molecules become dynamically arrested. As a result, in ternary systems, simultaneous additions of Whi3 and pairs of distinct RNA molecules lead to well-mixed condensates, whereas delayed addition of an RNA component results in compositional distinctness. Therefore, compositional identities of condensates can be achieved via dynamical control, being driven, at least partially, by the dynamical arrest of RNA molecules. Finally, we show that synchronizing the production of different RNAs leads to more well-mixed, as opposed to compositionally distinct condensates in vivo.

Suggested Citation

  • Andrew Z. Lin & Kiersten M. Ruff & Furqan Dar & Ameya Jalihal & Matthew R. King & Jared M. Lalmansingh & Ammon E. Posey & Nadia A. Erkamp & Ian Seim & Amy S. Gladfelter & Rohit V. Pappu, 2023. "Dynamical control enables the formation of demixed biomolecular condensates," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43489-4
    DOI: 10.1038/s41467-023-43489-4
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    References listed on IDEAS

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    1. Mina Farag & Wade M. Borcherds & Anne Bremer & Tanja Mittag & Rohit V. Pappu, 2023. "Phase separation of protein mixtures is driven by the interplay of homotypic and heterotypic interactions," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Yifeng Qi & Bin Zhang, 2021. "Chromatin network retards nucleoli coalescence," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    3. Taranpreet Kaur & Muralikrishna Raju & Ibraheem Alshareedah & Richoo B. Davis & Davit A. Potoyan & Priya R. Banerjee, 2021. "Sequence-encoded and composition-dependent protein-RNA interactions control multiphasic condensate morphologies," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    4. Nicola Galvanetto & Miloš T. Ivanović & Aritra Chowdhury & Andrea Sottini & Mark F. Nüesch & Daniel Nettels & Robert B. Best & Benjamin Schuler, 2023. "Extreme dynamics in a biomolecular condensate," Nature, Nature, vol. 619(7971), pages 876-883, July.
    5. Joshua A. Riback & Lian Zhu & Mylene C. Ferrolino & Michele Tolbert & Diana M. Mitrea & David W. Sanders & Ming-Tzo Wei & Richard W. Kriwacki & Clifford P. Brangwynne, 2020. "Composition-dependent thermodynamics of intracellular phase separation," Nature, Nature, vol. 581(7807), pages 209-214, May.
    6. Georg Krainer & Timothy J. Welsh & Jerelle A. Joseph & Jorge R. Espinosa & Sina Wittmann & Ella Csilléry & Akshay Sridhar & Zenon Toprakcioglu & Giedre Gudiškytė & Magdalena A. Czekalska & William E. , 2021. "Reentrant liquid condensate phase of proteins is stabilized by hydrophobic and non-ionic interactions," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    7. Pilong Li & Sudeep Banjade & Hui-Chun Cheng & Soyeon Kim & Baoyu Chen & Liang Guo & Marc Llaguno & Javoris V. Hollingsworth & David S. King & Salman F. Banani & Paul S. Russo & Qiu-Xing Jiang & B. Tra, 2012. "Phase transitions in the assembly of multivalent signalling proteins," Nature, Nature, vol. 483(7389), pages 336-340, March.
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