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Review
. 2019 Nov 1;5(4):50.
doi: 10.3390/ncrna5040050.

Evidence for and against Liquid-Liquid Phase Separation in the Nucleus

Peng A  1 , Stephanie C Weber  2   3
Affiliations
Review

Evidence for and against Liquid-Liquid Phase Separation in the Nucleus

Peng A et al. Noncoding RNA. .

Abstract

Enclosed by two membranes, the nucleus itself is comprised of various membraneless compartments, including nuclear bodies and chromatin domains. These compartments play an important though still poorly understood role in gene regulation. Significant progress has been made in characterizing the dynamic behavior of nuclear compartments and liquid-liquid phase separation (LLPS) has emerged as a prominent mechanism governing their assembly. However, recent work reveals that certain nuclear structures violate key predictions of LLPS, suggesting that alternative mechanisms likely contribute to nuclear organization. Here, we review the evidence for and against LLPS for several nuclear compartments and discuss experimental strategies to identify the mechanism(s) underlying their assembly. We propose that LLPS, together with multiple modes of protein-nucleic acid binding, drive spatiotemporal organization of the nucleus and facilitate functional diversity among nuclear compartments.

Keywords: heterochromatin; liquid-liquid phase separation; nuclear bodies; nucleolus; paraspeckles; replication compartments; transcriptional condensates.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Membraneless compartments can form through at least three distinct mechanisms: (A) binding, (B) bridging, or (C) liquid-liquid phase separation.
Figure 2
Figure 2
The nucleus contains many different membraneless structures, including the nucleolus (orange), constitutive heterochromatin compartments (yellow), paraspeckles (green) and transcriptional condensates (blue), which have all been proposed to assemble through liquid-liquid phase separation (LLPS). Replication compartments (purple) form following infection by herpes simplex virus.
Figure 3
Figure 3
Concentration dependence and diffusion across boundary represent useful criteria for distinguishing among various mechanisms for nuclear compartmentalization. (A) Each model predicts a distinct relationship between compartment size and component concentration. (B) LLPS can buffer the nucleoplasmic concentration, while binding and bridging mechanisms cannot. (C) Inert probes freely diffuse through compartments formed by binding or bridging, but their mobility is hindered by the phase boundary. (D) Component molecules move similarly to inert probes except when bound to the polymer scaffold. (E) Despite their spherical shape and molecular dynamics, replication compartments and paraspeckles are not consistent with LLPS. Images are reprinted from refs. [33,40,61] under the Creative Commons license: http://creativecommons.org/licenses/by/4.0/.
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