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Cells
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Nucleolar Organization and Functions in Health and Disease II
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Nucleolar Organization and Functions in Health and Disease II

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Nuclei: Function, Transport and Receptors".

Deadline for manuscript submissions: closed (15 November 2021) | Viewed by 13982

Special Issue Editors

Prof. Dr. Ursula Stochaj

E-Mail Website
Guest Editor
Department of Physiology, McGill University, Montreal, QC, Canada
Interests: nuclear envelope; nuclear lamina; nucleolus; RNA granules; stress responses; stress granules; molecular chaperones; cell signaling; AMP kinase; aging; senescence; nanobiomedicine; quantitative microscopy; high-throughput screening
Special Issues, Collections and Topics in MDPI journals
Dr. Mirek Dundr

E-Mail Website
Guest Editor
Center for Cancer Cell Biology, Chicago Medical School, Chicago, IL, USA
Interests: nuclear organization and architecture; gene expression and genome organization; nuclear biomolecular condensates; RNA transcription and processing, nucleolus; Cajal body; cancer, phase separation, quantitative microscopy

Special Issue Information

Dear Colleagues,

The nucleolus is the largest membrane-less compartment located within the nucleus of eukaryotic cells. It forms around the tandemly repeated ribosomal DNA genes, where it coordinates the transcription, processing, folding, and packaging of ribosomal RNA to produce pre-ribosomal subunits. Recent efforts to characterize the biophysical properties of the nucleolus have transformed our understanding of the assembly and organization of this dynamic compartment. Indeed, soluble macromolecules condense from the nucleoplasm to form nucleoli through a process called liquid–liquid phase separation. Individual nucleolar components rapidly exchange with the nucleoplasm but also form distinct nucleolar subcompartments. In addition to its essential role in ribosome biogenesis, the nucleolus regulates many aspects of cell physiology, including cell cycle progression, stress responses, senescence, lifespan, virus infections, and other health conditions. Accordingly, the nucleolus is implicated in several human diseases and disorders, including premature aging syndromes, Diamond–Blackfan anemia, and various forms of cancer.

This Special Issue will highlight new insights into the physical and molecular mechanisms that control the dynamic architecture and diverse functions of the nucleolus, and how they are impaired by disease. We invite contributions that cover the various aspects of nucleolar biology and their implications for human health. Manuscripts that apply interdisciplinary or quantitative approaches to study the various aspects of nucleolar assembly, mechanistic principles of substructural organization in health and disease, and the functional interplay among the many nucleolar functions are particularly welcome.

Prof. Dr. Ursula Stochaj
Dr. Mirek Dundr
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Nucleolus
  • Ribosome biogenesis
  • Pre-rRNA processing
  • Phase separation
  • Biological condensate
  • Stress response
  • Aging
  • Ribosomopathy
  • Cancer

Published Papers (4 papers)

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Research

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16 pages, 27219 KiB  
Article
Fine-Tuning of mTOR mRNA and Nucleolin Complexes by SMN
by Francesca Gabanella, Christian Barbato, Marco Fiore, Carla Petrella, Marco de Vincentiis, Antonio Greco, Antonio Minni, Nicoletta Corbi, Claudio Passananti and Maria Grazia Di Certo
Cells 2021, 10(11), 3015; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10113015 - 04 Nov 2021
Cited by 9 | Viewed by 2343
Abstract
Increasing evidence points to the Survival Motor Neuron (SMN) protein as a key determinant of translation pathway. Besides its role in RNA processing and sorting, several works support a critical implication of SMN in ribosome biogenesis. We previously showed that SMN binds ribosomal [...] Read more.
Increasing evidence points to the Survival Motor Neuron (SMN) protein as a key determinant of translation pathway. Besides its role in RNA processing and sorting, several works support a critical implication of SMN in ribosome biogenesis. We previously showed that SMN binds ribosomal proteins (RPs) as well as their encoding transcripts, ensuring an appropriate level of locally synthesized RPs. SMN impacts the translation machinery in both neural and non-neural cells, in agreement with the concept that SMN is an essential protein in all cell types. Here, we further assessed the relationship between SMN and translation-related factors in immortalized human fibroblasts. We focused on SMN-nucleolin interaction, keeping in mind that nucleolin is an RNA-binding protein, highly abundant within the nucleolus, that exhibits a central role in ribosomes production. Nucleolin may also affects translation network by binding the mammalian target of rapamycin (mTOR) mRNA and promoting its local synthesis. In this regard, for the first time we provided evidence that SMN protein itself associates with mTOR transcript. Collectively, we found that: (1) SMN coexists with nucleolin–mTOR mRNA complexes at subcellular level; (2) SMN deficiency impairs nucleolar compartmentalization of nucleolin, and (3) this event correlates with the nuclear retention of mTOR mRNA. These findings suggest that SMN may regulate not only structural components of translation machinery, but also their upstream regulating factors. Full article
(This article belongs to the Special Issue Nucleolar Organization and Functions in Health and Disease II)
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Review

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15 pages, 2208 KiB  
Review
Regulation of Nucleolar Activity by MYC
by Isabella N. Brown, M. Carmen Lafita-Navarro and Maralice Conacci-Sorrell
Cells 2022, 11(3), 574; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11030574 - 07 Feb 2022
Cited by 7 | Viewed by 2927
Abstract
The nucleolus harbors the machinery necessary to produce new ribosomes which are critical for protein synthesis. Nucleolar size, shape, and density are highly dynamic and can be adjusted to accommodate ribosome biogenesis according to the needs for protein synthesis. In cancer, cells undergo [...] Read more.
The nucleolus harbors the machinery necessary to produce new ribosomes which are critical for protein synthesis. Nucleolar size, shape, and density are highly dynamic and can be adjusted to accommodate ribosome biogenesis according to the needs for protein synthesis. In cancer, cells undergo continuous proliferation; therefore, nucleolar activity is elevated due to their high demand for protein synthesis. The transcription factor and universal oncogene MYC promotes nucleolar activity by enhancing the transcription of ribosomal DNA (rDNA) and ribosomal proteins. This review summarizes the importance of nucleolar activity in mammalian cells, MYC’s role in nucleolar regulation in cancer, and discusses how a better understanding (and the potential inhibition) of aberrant nucleolar activity in cancer cells could lead to novel therapeutics. Full article
(This article belongs to the Special Issue Nucleolar Organization and Functions in Health and Disease II)
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16 pages, 4005 KiB  
Review
Human rDNA and Cancer
by Evgeny Smirnov, Nikola Chmúrčiaková and Dušan Cmarko
Cells 2021, 10(12), 3452; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10123452 - 08 Dec 2021
Cited by 14 | Viewed by 3664
Abstract
In human cells, each rDNA unit consists of the ~13 kb long ribosomal part and ~30 kb long intergenic spacer (IGS). The ribosomal part, transcribed by RNA polymerase I (pol I), includes genes coding for 18S, 5.8S, and 28S RNAs of the ribosomal [...] Read more.
In human cells, each rDNA unit consists of the ~13 kb long ribosomal part and ~30 kb long intergenic spacer (IGS). The ribosomal part, transcribed by RNA polymerase I (pol I), includes genes coding for 18S, 5.8S, and 28S RNAs of the ribosomal particles, as well as their four transcribed spacers. Being highly repetitive, intensively transcribed, and abundantly methylated, rDNA is a very fragile site of the genome, with high risk of instability leading to cancer. Multiple small mutations, considerable expansion or contraction of the rDNA locus, and abnormally enhanced pol I transcription are usual symptoms of transformation. Recently it was found that both IGS and the ribosomal part of the locus contain many functional/potentially functional regions producing non-coding RNAs, which participate in the pol I activity regulation, stress reactions, and development of the malignant phenotype. Thus, there are solid reasons to believe that rDNA locus plays crucial role in carcinogenesis. In this review we discuss the data concerning the human rDNA and its closely associated factors as both targets and drivers of the pathways essential for carcinogenesis. We also examine whether variability in the structure of the locus may be blamed for the malignant transformation. Additionally, we consider the prospects of therapy focused on the activity of rDNA. Full article
(This article belongs to the Special Issue Nucleolar Organization and Functions in Health and Disease II)
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19 pages, 660 KiB  
Review
Manipulation of Cellular Processes via Nucleolus Hijaking in the Course of Viral Infection in Mammals
by Olga V. Iarovaia, Elena S. Ioudinkova, Artem K. Velichko and Sergey V. Razin
Cells 2021, 10(7), 1597; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10071597 - 25 Jun 2021
Cited by 14 | Viewed by 4180
Abstract
Due to their exceptional simplicity of organization, viruses rely on the resources, molecular mechanisms, macromolecular complexes, regulatory pathways, and functional compartments of the host cell for an effective infection process. The nucleolus plays an important role in the process of interaction between the [...] Read more.
Due to their exceptional simplicity of organization, viruses rely on the resources, molecular mechanisms, macromolecular complexes, regulatory pathways, and functional compartments of the host cell for an effective infection process. The nucleolus plays an important role in the process of interaction between the virus and the infected cell. The interactions of viral proteins and nucleic acids with the nucleolus during the infection process are universal phenomena and have been described for almost all taxonomic groups. During infection, proteins of the nucleolus in association with viral components can be directly used for the processes of replication and transcription of viral nucleic acids and the assembly and transport of viral particles. In the course of a viral infection, the usurpation of the nucleolus functions occurs and the usurpation is accompanied by profound changes in ribosome biogenesis. Recent studies have demonstrated that the nucleolus is a multifunctional and dynamic compartment. In addition to the biogenesis of ribosomes, it is involved in regulating the cell cycle and apoptosis, responding to cellular stress, repairing DNA, and transcribing RNA polymerase II-dependent genes. A viral infection can be accompanied by targeted transport of viral proteins to the nucleolus, massive release of resident proteins of the nucleolus into the nucleoplasm and cytoplasm, the movement of non-nucleolar proteins into the nucleolar compartment, and the temporary localization of viral nucleic acids in the nucleolus. The interaction of viral and nucleolar proteins interferes with canonical and non-canonical functions of the nucleolus and results in a change in the physiology of the host cell: cell cycle arrest, intensification or arrest of ribosome biogenesis, induction or inhibition of apoptosis, and the modification of signaling cascades involved in the stress response. The nucleolus is, therefore, an important target during viral infection. In this review, we discuss the functional impact of viral proteins and nucleic acid interaction with the nucleolus during infection. Full article
(This article belongs to the Special Issue Nucleolar Organization and Functions in Health and Disease II)
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