Review
. 2019 Aug; 8(8):869.
doi: 10.3390/cells8080869.

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

Carl C Correll 1 Jiri Bartek 2 Miroslav Dundr 3 
Affiliations
  • PMID: 31405125
  •     111 References
  •     17 citations

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.

Keywords: genome instability; links to diseases; nucleolus; phase separation; pre-rRNA processing; rDNA genes; ribosomal genes; ribosome biogenesis.

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Francisco Guillen-Chable, Ulises Rodríguez Corona, +7 authors, Enrique Castano.
Cells, 2020 May 10; 9(5). PMID: 32384686    Free PMC article.
Opposite regulation of piRNAs, rRNAs and miRNAs in the blood after subarachnoid hemorrhage.
Rafal Morga, Malgorzata Borczyk, +7 authors, Joanna Pera.
J Mol Med (Berl), 2020 May 20; 98(6). PMID: 32424559    Free PMC article.
Nuclear hubs built on RNAs and clustered organization of the genome.
Kelly P Smith, Lisa L Hall, Jeanne B Lawrence.
Curr Opin Cell Biol, 2020 Apr 08; 64. PMID: 32259767    Free PMC article.
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The Existence and Localization of Nuclear snoRNAs in Arabidopsis thaliana Revisited.
Deniz Streit, Thiruvenkadam Shanmugam, +2 authors, Enrico Schleiff.
Plants (Basel), 2020 Aug 19; 9(8). PMID: 32806552    Free PMC article.
Recent advances in the nucleolar responses to DNA double-strand breaks.
Lea Milling Korsholm, Zita Gál, +4 authors, Dorthe Helena Larsen.
Nucleic Acids Res, 2020 Aug 29; 48(17). PMID: 32857853    Free PMC article.
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Roles of ASYMMETRIC LEAVES2 (AS2) and Nucleolar Proteins in the Adaxial-Abaxial Polarity Specification at the Perinucleolar Region in Arabidopsis.
Hidekazu Iwakawa, Hiro Takahashi, Yasunori Machida, Chiyoko Machida.
Int J Mol Sci, 2020 Oct 08; 21(19). PMID: 33022996    Free PMC article.
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Inhibition of the de novo pyrimidine biosynthesis pathway limits ribosomal RNA transcription causing nucleolar stress in glioblastoma cells.
M Carmen Lafita-Navarro, Niranjan Venkateswaran, +7 authors, Maralice Conacci-Sorrell.
PLoS Genet, 2020 Nov 18; 16(11). PMID: 33201894    Free PMC article.
Coordination of transcription, processing, and export of highly expressed RNAs by distinct biomolecular condensates.
Alexander M Ishov, Aishwarya Gurumurthy, Jörg Bungert.
Emerg Top Life Sci, 2020 Apr 28; 4(3). PMID: 32338276    Free PMC article.
Sequence-encoded and composition-dependent protein-RNA interactions control multiphasic condensate morphologies.
Taranpreet Kaur, Muralikrishna Raju, +3 authors, Priya R Banerjee.
Nat Commun, 2021 Feb 10; 12(1). PMID: 33558506    Free PMC article.
Methylation of 45S Ribosomal DNA (rDNA) Is Associated with Cancer and Aging in Humans.
Fengqing Shao, Xiaoqi Liu, +2 authors, Wencai Wang.
Int J Genomics, 2021 Feb 13; 2021. PMID: 33575316    Free PMC article.
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The Role of TCOF1 Gene in Health and Disease: Beyond Treacher Collins Syndrome.
Małgorzata Grzanka, Agnieszka Piekiełko-Witkowska.
Int J Mol Sci, 2021 Apr 04; 22(5). PMID: 33804586    Free PMC article.
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Phase separation of DNA: From past to present.
John T King, Anisha Shakya.
Biophys J, 2021 Feb 15; 120(7). PMID: 33582138    Free PMC article.
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The rDNA is biomolecular condensate formed by polymer-polymer phase separation and is sequestered in the nucleolus by transcription and R-loops.
Josh Lawrimore, Daniel Kolbin, +5 authors, Kerry Bloom.
Nucleic Acids Res, 2021 Apr 10; 49(8). PMID: 33836082    Free PMC article.