Coexisting liquid phases underlie nucleolar sub-compartments

By Marina Feric, Nilesh Vaidya, T. Harmon, Diana M. Mitrea, Lian Zhu, Tiffany M. Richardson, Richard W. Kriwacki, Rohit V. Pappu, C. Brangwynne. Cell, 2016

1,722 citations recorded by the source corpus.

Summary The nucleolus and other ribonucleoprotein (RNP) bodies are membrane-less organelles that appear to assemble through phase separation of their molecular components. However, many such RNP bodies contain internal sub-compartments, and the mechanism of their formation remains unclear. Here, we combine in vivo and in vitro studies, together with computational modeling, to show that sub-compartments within the nucleolus represent distinct, coexisting liquid phases. Consistent with their in vivo immiscibility, purified nucleolar proteins phase separate into droplets containing distinct non-coalescing phases that are remarkably similar to nucleoli in vivo. This layered droplet organization is caused by differences in the biophysical properties of the phases – particularly droplet surface tension – which arises from sequence-encoded features of their macromolecular components. These results suggest that phase separation can give rise to multilayered liquids that may facilitate sequential RNA processing reactions in a variety of RNP bodies.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a7b31cc1a674220518c16095c54ec76723cfb9fa

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Citations in the corpus

Pathways of cellular proteostasis in aging and disease (2018, background): “As shown recently, such proteins often have the ability to undergo liquid–liquid phase transitions (Feric et al., 2016), forming dynamic droplet-like compartments in the nucleus and cytosol that participate in RNA metabolism, ribosome biogenesis, cell signaling, and other processes (Banani et al.”
Stress-triggered phase separation is an adaptive, evolutionarily tuned response (2017, background): “Groundbreaking work has focused on phase separation as a mechanism to compartmentalize an otherwise-well-mixed milieu (Feric et al., 2016; Hyman et al., 2014; Li et al., 2012; Su et al., 2016).”
Sequence determinants of protein phase behavior from a coarse-grained model (2017, background): “These 4 organelles include processing bodies [4], stress granules [3, 5–7] and germ granules [8, 9] 5 in the cytoplasm, and nucleoli [10] and nuclear speckles [11] in the nucleus.”
DEAD-Box Helicases: Sensors, Regulators, and Effectors for Antiviral Defense (2020, background): “Nucleoli form as sites of concentrated processing factors around clusters of rDNA genes, and liquid–liquid phase separation drives the organization of subcompartments in which rRNA is cleaved and modified [49,50].”
Compositional Control of Phase-Separated Cellular Bodies (2016, neutral): “Finally, several cellular bodies contain subcompartments (condensed phases within the primary condensed phase) and thus are not simple droplet/bulk systems (Brangwynne et al., 2011; Feric et al., 2016; Jain et al., 2016; Wang et al., 2014).”
Ki-67: more than a proliferation marker (2018, background): “Analyses in Xenopus oocyte nuclei and Drosophila embryos reveal that the internal organization of nucleoli depends on liquid-liquid phase separation (Feric et al. 2016).”
Spatiotemporal control of intracellular phase transitions using light-activated optoDroplets (2016, positive): “For example, both nucleoli and stress granules have recently been reported to have a core-shell structure, where gel-like cores are engulfed by a dynamic liquid-like shell ((Jain et al., 2016), (Feric et al., 2016)).”
Protein Phase Separation: A New Phase in Cell Biology (2018, background): “These results point to a complex internal organization of SGs, a picture that, given recent work, is likely true for other membraneless organelles as well [24,25,68].”