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Sequence-encoded and composition-dependent protein-RNA interactions control multiphasic condensate morphologies

Author

Listed:
  • Taranpreet Kaur

    (University at Buffalo)

  • Muralikrishna Raju

    (Iowa State University)

  • Ibraheem Alshareedah

    (University at Buffalo)

  • Richoo B. Davis

    (University at Buffalo)

  • Davit A. Potoyan

    (Iowa State University)

  • Priya R. Banerjee

    (University at Buffalo)

Abstract

Multivalent protein-protein and protein-RNA interactions are the drivers of biological phase separation. Biomolecular condensates typically contain a dense network of multiple proteins and RNAs, and their competing molecular interactions play key roles in regulating the condensate composition and structure. Employing a ternary system comprising of a prion-like polypeptide (PLP), arginine-rich polypeptide (RRP), and RNA, we show that competition between the PLP and RNA for a single shared partner, the RRP, leads to RNA-induced demixing of PLP-RRP condensates into stable coexisting phases—homotypic PLP condensates and heterotypic RRP-RNA condensates. The morphology of these biphasic condensates (non-engulfing/ partial engulfing/ complete engulfing) is determined by the RNA-to-RRP stoichiometry and the hierarchy of intermolecular interactions, providing a glimpse of the broad range of multiphasic patterns that are accessible to these condensates. Our findings provide a minimal set of physical rules that govern the composition and spatial organization of multicomponent and multiphasic biomolecular condensates.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21089-4
    DOI: 10.1038/s41467-021-21089-4
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    Cited by:

    1. Nadia A. Erkamp & Tomas Sneideris & Hannes Ausserwöger & Daoyuan Qian & Seema Qamar & Jonathon Nixon-Abell & Peter George-Hyslop & Jeremy D. Schmit & David A. Weitz & Tuomas P. J. Knowles, 2023. "Spatially non-uniform condensates emerge from dynamically arrested phase separation," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    2. Anamika Avni & Ashish Joshi & Anuja Walimbe & Swastik G. Pattanashetty & Samrat Mukhopadhyay, 2022. "Single-droplet surface-enhanced Raman scattering decodes the molecular determinants of liquid-liquid phase separation," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Richoo B. Davis & Anushka Supakar & Aishwarya Kanchi Ranganath & Mahdi Muhammad Moosa & Priya R. Banerjee, 2024. "Heterotypic interactions can drive selective co-condensation of prion-like low-complexity domains of FET proteins and mammalian SWI/SNF complex," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Aishwarya Agarwal & Lisha Arora & Sandeep K. Rai & Anamika Avni & Samrat Mukhopadhyay, 2022. "Spatiotemporal modulations in heterotypic condensates of prion and α-synuclein control phase transitions and amyloid conversion," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    5. Ashish Joshi & Anuja Walimbe & Anamika Avni & Sandeep K. Rai & Lisha Arora & Snehasis Sarkar & Samrat Mukhopadhyay, 2023. "Single-molecule FRET unmasks structural subpopulations and crucial molecular events during FUS low-complexity domain phase separation," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    6. Ibraheem Alshareedah & Mahdi Muhammad Moosa & Matthew Pham & Davit A. Potoyan & Priya R. Banerjee, 2021. "Programmable viscoelasticity in protein-RNA condensates with disordered sticker-spacer polypeptides," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    7. Jaewoon Jung & Cheng Tan & Yuji Sugita, 2024. "GENESIS CGDYN: large-scale coarse-grained MD simulation with dynamic load balancing for heterogeneous biomolecular systems," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    8. 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.
    9. 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.

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