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The Nucleolus: A Multiphase Condensate Balancing Ribosome Synthesis and Translational Capacity in Health, Aging and Ribosomopathies

1
Center for Proteomics and Molecular Therapeutics, Rosalind Franklin University of Medicine & Science, North Chicago, IL 60064, USA
2
Danish Cancer Society Research Center, Genome Integrity Unit, DK-2100 Copenhagen, Denmark
3
Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Science for Life Laboratory, Karolinska Institute, SE-171 77 Stockholm, Sweden
4
Center for Cancer Cell Biology Immunology and Infection, Rosalind Franklin University of Medicine & Science, North Chicago, IL 60064, USA
*
Authors to whom correspondence should be addressed.
Cells 2019, 8(8), 869; https://doi.org/10.3390/cells8080869
Received: 14 June 2019 / Revised: 31 July 2019 / Accepted: 6 August 2019 / Published: 10 August 2019
(This article belongs to the Special Issue Nucleolar Organization and Functions in Health and Disease)
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Abstract

The nucleolus is the largest membrane-less structure in the eukaryotic nucleus. It is involved in the biogenesis of ribosomes, essential macromolecular machines responsible for synthesizing all proteins required by the cell. The assembly of ribosomes is evolutionarily conserved and is the most energy-consuming cellular process needed for cell growth, proliferation, and homeostasis. Despite the significance of this process, the intricate pathophysiological relationship between the nucleolus and protein synthesis has only recently begun to emerge. Here, we provide perspective on new principles governing nucleolar formation and the resulting multiphase organization driven by liquid-liquid phase separation. With recent advances in the structural analysis of ribosome formation, we highlight the current understanding of the step-wise assembly of pre-ribosomal subunits and the quality control required for proper function. Finally, we address how aging affects ribosome genesis and how genetic defects in ribosome formation cause ribosomopathies, complex diseases with a predisposition to cancer. View Full-Text
Keywords: genome instability; nucleolus; phase separation; pre-rRNA processing; rDNA genes; ribosome biogenesis; ribosomal genes; links to diseases genome instability; nucleolus; phase separation; pre-rRNA processing; rDNA genes; ribosome biogenesis; ribosomal genes; links to diseases
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Correll, C.C.; Bartek, J.; Dundr, M. The Nucleolus: A Multiphase Condensate Balancing Ribosome Synthesis and Translational Capacity in Health, Aging and Ribosomopathies. Cells 2019, 8, 869.

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