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Intermolecular energy migration via homoFRET captures the modulation in the material property of phase-separated biomolecular condensates

Author

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  • Ashish Joshi

    (Indian Institute of Science Education and Research (IISER) Mohali
    Indian Institute of Science Education and Research (IISER) Mohali)

  • Anuja Walimbe

    (Indian Institute of Science Education and Research (IISER) Mohali
    Indian Institute of Science Education and Research (IISER) Mohali)

  • Snehasis Sarkar

    (Indian Institute of Science Education and Research (IISER) Mohali
    Indian Institute of Science Education and Research (IISER) Mohali)

  • Lisha Arora

    (Indian Institute of Science Education and Research (IISER) Mohali
    Indian Institute of Science Education and Research (IISER) Mohali)

  • Gaganpreet Kaur

    (Indian Institute of Science Education and Research (IISER) Mohali)

  • Prince Jhandai

    (Indian Institute of Science Education and Research (IISER) Mohali
    Oklahoma State University)

  • Dhruba Chatterjee

    (Indian Institute of Science Education and Research (IISER) Mohali
    Indian Institute of Science Education and Research (IISER) Mohali)

  • Indranil Banerjee

    (Indian Institute of Science Education and Research (IISER) Mohali)

  • Samrat Mukhopadhyay

    (Indian Institute of Science Education and Research (IISER) Mohali
    Indian Institute of Science Education and Research (IISER) Mohali
    Indian Institute of Science Education and Research (IISER) Mohali)

Abstract

Physical properties of biomolecular condensates formed via phase separation of proteins and nucleic acids are associated with cell physiology and disease. Condensate properties can be regulated by several cellular factors including post-translational modifications. Here, we introduce an application of intermolecular energy migration via homo-FRET (Förster resonance energy transfer), a nanometric proximity ruler, to study the modulation in short- and long-range protein-protein interactions leading to the changes in the physical properties of condensates of fluorescently-tagged FUS (Fused in Sarcoma) that is associated with the formation of cytoplasmic and nuclear membraneless organelles. We show that homoFRET captures modulations in condensate properties of FUS by RNA, ATP, and post-translational arginine methylation. We also extend the homoFRET methodology to study the in-situ formation of cytoplasmic stress granules in mammalian cells. Our studies highlight the broad applicability of homoFRET as a potent generic tool for studying intracellular phase transitions involved in function and disease.

Suggested Citation

  • Ashish Joshi & Anuja Walimbe & Snehasis Sarkar & Lisha Arora & Gaganpreet Kaur & Prince Jhandai & Dhruba Chatterjee & Indranil Banerjee & Samrat Mukhopadhyay, 2024. "Intermolecular energy migration via homoFRET captures the modulation in the material property of phase-separated biomolecular condensates," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53494-w
    DOI: 10.1038/s41467-024-53494-w
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