The Experts below are selected from a list of 297 Experts worldwide ranked by ideXlab platform
Clifford P. Brangwynne - One of the best experts on this subject based on the ideXlab platform.
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The Nucleolus as a multiphase liquid condensate.
Nature Reviews Molecular Cell Biology, 2020Co-Authors: Denis L.j. Lafontaine, Joshua A. Riback, Rümeyza Bascetin, Clifford P. BrangwynneAbstract:The Nucleolus is the most prominent nuclear body and serves a fundamentally important biological role as a site of ribonucleoprotein particle assembly, primarily dedicated to ribosome biogenesis. Despite being one of the first intracellular structures visualized historically, the biophysical rules governing its assembly and function are only starting to become clear. Recent studies have provided increasing support for the concept that the Nucleolus represents a multilayered biomolecular condensate, whose formation by liquid–liquid phase separation (LLPS) facilitates the initial steps of ribosome biogenesis and other functions. Here, we review these biophysical insights in the context of the molecular and cell biology of the Nucleolus. We discuss how nucleolar function is linked to its organization as a multiphase condensate and how dysregulation of this organization could provide insights into still poorly understood aspects of Nucleolus-associated diseases, including cancer, ribosomopathies and neurodegeneration as well as ageing. We suggest that the LLPS model provides the starting point for a unifying quantitative framework for the assembly, structural maintenance and function of the Nucleolus, with implications for gene regulation and ribonucleoprotein particle assembly throughout the nucleus. The LLPS concept is also likely useful in designing new therapeutic strategies to target nucleolar dysfunction. The Nucleolus is a membraneless organelle involved in ribonucleoprotein assembly, including ribosome biogenesis. Recent evidence indicates that the Nucleolus is a biomolecular condensate that forms via liquid–liquid phase separation (LLPS), and insights from studies within the LLPS framework are increasing our understanding of the relationship between nucleolar structure and function.
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controlling the material properties and rrna processing function of the Nucleolus using light
Proceedings of the National Academy of Sciences of the United States of America, 2019Co-Authors: Lian Zhu, Denis L.j. Lafontaine, Clifford P. Brangwynne, Tiffany M Richardson, Ludivine Wacheul, Mingtzo Wei, Marina Feric, Gena WhitneyAbstract:The Nucleolus is a prominent nuclear condensate that plays a central role in ribosome biogenesis by facilitating the transcription and processing of nascent ribosomal RNA (rRNA). A number of studies have highlighted the active viscoelastic nature of the Nucleolus, whose material properties and phase behavior are a consequence of underlying molecular interactions. However, the ways in which the material properties of the Nucleolus impact its function in rRNA biogenesis are not understood. Here we utilize the Cry2olig optogenetic system to modulate the viscoelastic properties of the Nucleolus. We show that above a threshold concentration of Cry2olig protein, the Nucleolus can be gelled into a tightly linked, low mobility meshwork. Gelled nucleoli no longer coalesce and relax into spheres but nonetheless permit continued internal molecular mobility of small proteins. These changes in nucleolar material properties manifest in specific alterations in rRNA processing steps, including a buildup of larger rRNA precursors and a depletion of smaller rRNA precursors. We propose that the flux of processed rRNA may be actively tuned by the cell through modulating nucleolar material properties, which suggests the potential of materials-based approaches for therapeutic intervention in ribosomopathies.
J. A. Hiscox - One of the best experts on this subject based on the ideXlab platform.
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The Nucleolus – a gateway to viral infection?
Archives of Virology, 2002Co-Authors: J. A. HiscoxAbstract:A number of viruses and viral proteins interact with a dynamic sub-nuclear structure called the Nucleolus. The Nucleolus is present during interphase in mammalian cells and is the site of ribosome biogenesis, and has been implicated in controlling regulatory processes such as the cell cycle. Viruses interact with the Nucleolus and its antigens; viral proteins co-localise with factors such as nucleolin, B23 and fibrillarin, and can cause their redistribution during infection. Viruses can use these components as part of their replication process, and also use the Nucleolus as a site of replication itself. Many of these properties are not restricted to any particular type of virus or replication mechanism, and examples of these processes can be found in DNA, RNA and retroviruses. Evidence suggests that viruses may target the Nucleolus and its components to favour viral transcription, translation and perhaps alter the cell cycle in order to promote virus replication. Autoimmunity to nucleolin and fibrillarin have been associated with a number of diseases, and by targeting the Nucleolus and displacing nucleolar antigens, virus infection might play a role in the initiation of these conditions.
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The Nucleolus--a gateway to viral infection?
Archives of Virology, 2002Co-Authors: J. A. HiscoxAbstract:A number of viruses and viral proteins interact with a dynamic sub-nuclear structure called the Nucleolus. The Nucleolus is present during interphase in mammalian cells and is the site of ribosome biogenesis, and has been implicated in controlling regulatory processes such as the cell cycle. Viruses interact with the Nucleolus and its antigens; viral proteins co-localise with factors such as nucleolin, B23 and fibrillarin, and can cause their redistribution during infection. Viruses can use these components as part of their replication process, and also use the Nucleolus as a site of replication itself. Many of these properties are not restricted to any particular type of virus or replication mechanism, and examples of these processes can be found in DNA, RNA and retroviruses. Evidence suggests that viruses may target the Nucleolus and its components to favour viral transcription, translation and perhaps alter the cell cycle in order to promote virus replication. Autoimmunity to nucleolin and fibrillarin have been associated with a number of diseases, and by targeting the Nucleolus and displacing nucleolar antigens, virus infection might play a role in the initiation of these conditions.
Craig S. Pikaard - One of the best experts on this subject based on the ideXlab platform.
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Identification of Nucleolus-Associated Chromatin Domains Reveals a Role for the Nucleolus in 3D Organization of the A. thaliana Genome
Cell Reports, 2016Co-Authors: Frederic Pontvianne, Marie-christine Carpentier, Nathalie Durut, Veronika Pavlištová, Karin Jaške, Šárka Schořová, Hugues Parrinello, Marine Rohmer, Craig S. Pikaard, Miloslava FojtováAbstract:The Nucleolus is the site of rRNA gene transcription,rRNA processing, and ribosome biogenesis. How-ever, the Nucleolus also plays additional roles in thecell. We isolated nucleoli using fluorescence-acti-vated cell sorting (FACS) and identified Nucleolus-associated chromatin domains (NADs) by deep seq-uencing, comparing wild-type plants and null mutantsfor the nucleolar protein NUCLEOLIN 1 (NUC1). NADsare primarily genomic regions with heterochromaticsignatures and include transposable elements (TEs),sub-telomeric regions, and mostly inactive protein-coding genes. However, NADs also include activer RNA genes and the entire short arm of chromosome4 adjacent to them. Innuc1null mutants, which alterrRNA gene expression and overall nucleolar structure,NADs are altered, telomere association with thenucle-olus is decreased, and telomeres become shorter.Collectively, our studies reveal roles for NUC1 and the Nucleolus in the spatial organization of chromosomes as well as telomere maintenance
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Identification of Nucleolus-Associated Chromatin Domains Reveals a Role for the Nucleolus in 3D Organization of the A. thaliana Genome.
Cell Reports, 2016Co-Authors: Frederic Pontvianne, Marie-christine Carpentier, Nathalie Durut, Veronika Pavlištová, Karin Jaške, Šárka Schořová, Hugues Parrinello, Marine Rohmer, Craig S. Pikaard, Miloslava FojtováAbstract:The Nucleolus is the site of rRNA gene transcription, rRNA processing, and ribosome biogenesis. However, the Nucleolus also plays additional roles in the cell. We isolated nucleoli using fluorescence-activated cell sorting (FACS) and identified Nucleolus-associated chromatin domains (NADs) by deep sequencing, comparing wild-type plants and null mutants for the nucleolar protein NUCLEOLIN 1 (NUC1). NADs are primarily genomic regions with heterochromatic signatures and include transposable elements (TEs), sub-telomeric regions, and mostly inactive protein-coding genes. However, NADs also include active rRNA genes and the entire short arm of chromosome 4 adjacent to them. In nuc1 null mutants, which alter rRNA gene expression and overall nucleolar structure, NADs are altered, telomere association with the Nucleolus is decreased, and telomeres become shorter. Collectively, our studies reveal roles for NUC1 and the Nucleolus in the spatial organization of chromosomes as well as telomere maintenance.
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natural variation in nucleolar dominance reveals the relationship between Nucleolus organizer chromatin topology and rrna gene transcription in arabidopsis
Proceedings of the National Academy of Sciences of the United States of America, 2003Co-Authors: Olga Pontes, Richard J Lawrence, Nuno Neves, Manuela Silva, Jeffrey Z Chen, Wanda Viegas, Craig S. PikaardAbstract:In genetic hybrids, Nucleolus formation on chromosomes inherited from only one parent is the epigenetic phenomenon, nucleolar dominance. By using Arabidopsis suecica, the allotetraploid hybrid of Arabidopsis thaliana and Arabidopsis arenosa, natural variation in nucleolar dominance was found to occur, providing a unique opportunity to examine homologous Nucleolus organizer regions (NORs) in their active and inactive states. In A. suecica strain LC1, NORs derived from A. arenosa are active, whereas A. thaliana-derived NORs are silenced. In A. suecica strain 9502, NORs of both parental species are active. When active, NORs are partially, but not fully, decondensed. Both active and inactive LC1 NORs colocalize with the Nucleolus, contradicting the long-standing assumption that rRNA gene transcription drives Nucleolus association. Collectively, these observations clarify the relationships among NOR chromatin topology, rRNA gene transcription, and NOR–Nucleolus associations. A. suecica strains LC1 and 9502 have each lost one pair of A. thaliana NORs during evolution, and amplified fragment-length polymorphism analysis further indicates that these strains are genetically very similar. These data suggest that nucleolar dominance can result from subtle genetic or epigenetic variation but is not a trait fundamental to a given interspecies hybrid combination.
Frederic Pontvianne - One of the best experts on this subject based on the ideXlab platform.
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Nucleolus-associated chromatin domains are maintained under heat stress, despite nucleolar reorganization in Arabidopsis thaliana
Journal of Plant Research, 2020Co-Authors: Ariadna Picart-picolo, Claire Picart, Nathalie Picault, Frederic PontvianneAbstract:Several layers of mechanisms participate in plant adaptation to heat-stress. For example, the plant metabolism switches from cell growth mode to stress adaptation mode. Ribosome biogenesis is one of the most energy costly pathways. That biogenesis process occurs in the Nucleolus, the largest nuclear compartment, whose structure is highly dependent on this pathway. We used a nucleolar marker to track the structure of the Nucleolus, and revealed a change in its sub-nucleolar distribution under heat stress. In addition, the Nucleolus is implicated in other cellular processes, such as genome organization within the nucleus. However, our analyses of Nucleolus-associated chromatin domains under heat stress did not reveal significant differences compared to the control plants, suggesting a lack of connection between two of the main functions of the Nucleolus: ribosome biogenesis and nuclear organization.
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Identification of Nucleolus-Associated Chromatin Domains Reveals a Role for the Nucleolus in 3D Organization of the A. thaliana Genome
Cell Reports, 2016Co-Authors: Frederic Pontvianne, Marie-christine Carpentier, Nathalie Durut, Veronika Pavlištová, Karin Jaške, Šárka Schořová, Hugues Parrinello, Marine Rohmer, Craig S. Pikaard, Miloslava FojtováAbstract:The Nucleolus is the site of rRNA gene transcription,rRNA processing, and ribosome biogenesis. How-ever, the Nucleolus also plays additional roles in thecell. We isolated nucleoli using fluorescence-acti-vated cell sorting (FACS) and identified Nucleolus-associated chromatin domains (NADs) by deep seq-uencing, comparing wild-type plants and null mutantsfor the nucleolar protein NUCLEOLIN 1 (NUC1). NADsare primarily genomic regions with heterochromaticsignatures and include transposable elements (TEs),sub-telomeric regions, and mostly inactive protein-coding genes. However, NADs also include activer RNA genes and the entire short arm of chromosome4 adjacent to them. Innuc1null mutants, which alterrRNA gene expression and overall nucleolar structure,NADs are altered, telomere association with thenucle-olus is decreased, and telomeres become shorter.Collectively, our studies reveal roles for NUC1 and the Nucleolus in the spatial organization of chromosomes as well as telomere maintenance
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Identification of Nucleolus-Associated Chromatin Domains Reveals a Role for the Nucleolus in 3D Organization of the A. thaliana Genome.
Cell Reports, 2016Co-Authors: Frederic Pontvianne, Marie-christine Carpentier, Nathalie Durut, Veronika Pavlištová, Karin Jaške, Šárka Schořová, Hugues Parrinello, Marine Rohmer, Craig S. Pikaard, Miloslava FojtováAbstract:The Nucleolus is the site of rRNA gene transcription, rRNA processing, and ribosome biogenesis. However, the Nucleolus also plays additional roles in the cell. We isolated nucleoli using fluorescence-activated cell sorting (FACS) and identified Nucleolus-associated chromatin domains (NADs) by deep sequencing, comparing wild-type plants and null mutants for the nucleolar protein NUCLEOLIN 1 (NUC1). NADs are primarily genomic regions with heterochromatic signatures and include transposable elements (TEs), sub-telomeric regions, and mostly inactive protein-coding genes. However, NADs also include active rRNA genes and the entire short arm of chromosome 4 adjacent to them. In nuc1 null mutants, which alter rRNA gene expression and overall nucleolar structure, NADs are altered, telomere association with the Nucleolus is decreased, and telomeres become shorter. Collectively, our studies reveal roles for NUC1 and the Nucleolus in the spatial organization of chromosomes as well as telomere maintenance.
Bernardo Lemos - One of the best experts on this subject based on the ideXlab platform.
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ribosomal dna and the Nucleolus as keystones of nuclear architecture organization and function
Trends in Genetics, 2019Co-Authors: Amanda V Cerqueira, Bernardo LemosAbstract:The multicopy ribosomal DNA (rDNA) array gives origin to the Nucleolus, a large nonmembrane-bound organelle that occupies a substantial volume within the cell nucleus. The rDNA/Nucleolus has emerged as a coordinating hub in which seemingly disparate cellular functions converge, and from which a variety of cellular and organismal phenotypes emerge. However, the role of the Nucleolus as a determinant and organizer of nuclear architecture and other epigenetic states of the genome is not well understood. We discuss the role of rDNA and the Nucleolus in nuclear organization and function – from Nucleolus-associated domains (NADs) to the regulation of imprinted loci and X chromosome inactivation, as well as rDNA contact maps that anchor and position the rDNA relative to the rest of the genome. The influence of the Nucleolus on nuclear organization undoubtedly modulates diverse biological processes from metabolism to cell proliferation, genome-wide gene expression, maintenance of epigenetic states, and aging.
