Rainbow Nucleus Charts Dynamic Interactome of Membrane-less Organelles

2025 · doi:10.1101/2025.05.14.654140
preprint OA: closed CC-BY-NC-ND-4.0
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The study developed a live-cell multi-spectral imaging method called “Rainbow Nucleus” to simultaneously visualize five types of nuclear membrane-less organelles (MLOs) and analyze how they interact. Using this approach, the authors found that some MLO interactions are stable (e.g., histone locus bodies with Cajal bodies) while others are transient (e.g., PML bodies with Cajal bodies), and that interactions are enriched among functionally related MLOs. They also report that inhibiting transcription completely rewires the MLO interaction network, indicating strong condition dependence. The paper is framed as providing initial glimpses of MLO interactome dynamics, and it explicitly highlights that the findings serve as a foundation for future work rather than a complete mechanistic model. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Summary Membrane-less organelles (MLOs) perform diverse cellular functions, but how they interact to coordinate these processes remains poorly understood. Here we constructed a “Rainbow Nucleus” cell line to simultaneously visualize five nuclear MLOs using multi-spectral live-cell imaging. We find that MLO interactions are not random: nuclear speckles serve as hubs, and functionally related MLOs interact more frequently than unrelated MLOs. While some interactions are stable, such as those between the histone locus bodies and Cajal bodies, others are transient, such as those between PML nuclear bodies and Cajal bodies. Single particle tracking revealed that stable contacts between Cajal bodies and nuclear speckles are functional, promoting the outward trafficking of small nuclear ribonucleoproteins from Cajal bodies. Finally, RNA Polymerase II-mediated transcription is required to organize the MLO interactome. Our study reveals a structured, transcription-dependent contact network among nuclear MLOs, laying the foundation for future cellular engineering efforts to modulate the MLO interactome.
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Abstract Membrane-less organelles (MLOs) perform diverse and important functions inside cells. However, how they interact with each other to carry out these functions collectively is unknown. Here we devised a multi-spectral imaging technique called “Rainbow Nucleus” to simultaneously visualize five nuclear MLOs using live-cell imaging. We find that while some interactions are stable, such as those between the histone locus bodies and Cajal bodies, others are transient, such as those between PML bodies and Cajal bodies. Furthermore, interactions among MLOs are not random: functionally related MLOs interact more frequently than unrelated MLOs, and these interactions completely rewire when we inhibit transcription. Our study provides first glimpses into how different MLOs interact with each other under different conditions, and lays the foundation for future cellular engineering efforts that modulate MLOs interactome to treat diseases. Competing Interest Statement The authors have declared no competing interest.

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License: CC-BY-NC-ND-4.0