RNA-mediated demixing transition of low-density condensates

Taehyun Kim, Jaeyoon Yoo, Sungho Do, Dong Soo Hwang, YongKeun Park and Yongdae Shin ()
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Taehyun Kim: Seoul National University
Jaeyoon Yoo: Seoul National University
Sungho Do: Seoul National University
Dong Soo Hwang: Pohang University of Science and Technology (POSTECH)
YongKeun Park: Korea Advanced Institute of Science and Technology (KAIST)
Yongdae Shin: Seoul National University

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Biomolecular condensates play a key role in organizing cellular reactions by concentrating a specific set of biomolecules. However, whether condensate formation is accompanied by an increase in the total mass concentration within condensates or by the demixing of already highly crowded intracellular components remains elusive. Here, using refractive index imaging, we quantify the mass density of several condensates, including nucleoli, heterochromatin, nuclear speckles, and stress granules. Surprisingly, the latter two condensates exhibit low densities with a total mass concentration similar to the surrounding cyto- or nucleoplasm. Low-density condensates display higher permeability to cellular protein probes. We find that RNA tunes the biomolecular density of condensates. Moreover, intracellular structures such as mitochondria heavily influence the way phase separation proceeds, impacting the localization, morphology, and growth of condensates. These findings favor a model where segregative phase separation driven by non-associative or repulsive molecular interactions together with RNA-mediated selective association of specific components can give rise to low-density condensates in the crowded cellular environment.

Date: 2023
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DOI: 10.1038/s41467-023-38118-z

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