The Dynamics of the Nucleolus

Leung, Anthony K.L.; Lamond, Angus I.

doi:10.1615/critreveukaryotgeneexpr.v13.i1.40

Cited by 83 publications

(63 citation statements)

References 85 publications

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“…The traditional view of nucleoli serving primarily as a factory for assembling ribosomes is rapidly moving toward a new level of complexity at the center of key regulatory pathways controlling important biological processes such as cell cycle, proliferation, stress response, and even cellular aging (34)(35)(36). The finding that perturbation of nucleolar activity by genetic ablation of ribosome biogenesis initiates neurodegeneration in adult mice by activation of an endogenous response leading to p53 activation (24) is one example of an emerging series of findings that support the idea that the nucleolus acts as a sensor of cellular stress (1,3,(25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

Nucleolar stress is an early response to myocardial damage involving nucleolar proteins nucleostemin and nucleophosmin

Avitabile

Bailey

Cottage

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Nucleolar stress, characterized by loss of nucleolar integrity, has not been described in the cardiac context. In addition to ribosome biogenesis, nucleoli are critical for control of cell proliferation and stress responses. Our group previously demonstrated induction of the nucleolar protein nucleostemin (NS) in response to cardiac pathological insult. NS interacts with nucleophosmin (NPM), a marker of nucleolar stress with cytoprotective properties. The dynamic behavior of NS and NPM reveal that nucleolar disruption is an early event associated with stress response in cardiac cells. Rapid translocation of NS and NPM to the nucleoplasm and suppression of new preribosomal RNA synthesis occurs in both neonatal rat cardiomyocytes (NRCM) and cardiac progenitor cells (CPC) upon exposure to doxorubicin or actinomycin D. Silencing of NS significantly increases cell death resulting from doxorubicin treatment in CPC, whereas NPM knockdown alone induces cell death. Overexpression of either NS or NPM significantly decreases caspase 8 activity in cultured cardiomyocytes challenged with doxorubicin. The presence of altered nucleolar structures resulting from myocardial infarction in mice supports the model of nucleolar stress as a general response to pathological injury. Collectively, these findings serve as the initial description of myocardial nucleolar stress and establish the postulate that nucleoli acts as sensors of stress, regulating the cellular response to pathological insults.nucleolus | rRNA | hypoxia | hypertrophy

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Section: Discussionmentioning

confidence: 99%

Nucleolar stress is an early response to myocardial damage involving nucleolar proteins nucleostemin and nucleophosmin

Avitabile

Bailey

Cottage

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…The most prominent feature of a eukaryotic nucleus during interphase is the nucleolus (Figure 1), a region that contains relatively little chromosomal DNA but is rich in RNAs, proteins and ribonucleoprotein particles, including the large and small ribosome subunits as they undergo assembly [1][2][3]. The location of a nucleolus is not determined randomly; instead its formation is determined by the position of a discrete chromosomal locus known as a nucleolus organizer region, or NOR [4].…”

Section: Large Scale Cytological Effects Of Rrna Gene Regulation: Nucmentioning

confidence: 99%

rRNA gene silencing and nucleolar dominance: Insights into a chromosome-scale epigenetic on/off switch

Preuss

Pikaard

2007

Biochimica et Biophysica Acta (BBA) - Gene Structure and Expres

135

105

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Ribosomal RNA (rRNA) gene transcription accounts for most of the RNA in prokaryotic and eukaryotic cells. In eukaryotes, there are hundreds (to thousands) of rRNA genes tandemly repeated head-to-tail within nucleolus organizer regions (NORs) that span millions of basepairs. These nucleolar rRNA genes are transcribed by RNA Polymerase I (Pol I) and their expression is regulated according to the physiological need for ribosomes. Regulation occurs at several levels, one of which is an epigenetic on/off switch that controls the number of active rRNA genes. Additional mechanisms then fine-tune transcription initiation and elongation rates to dictate the total amount of rRNA produced per gene. In this review, we focus on the DNA and histone modifications that comprise the epigenetic on/off switch. In both plants and animals, this system is important for controlling the dosage of active rRNA genes. The dosage control system is also responsible for the chromatinmediated silencing of one parental set of rRNA genes in genetic hybrids, a large-scale epigenetic phenomenon known as nucleolar dominance.Keywords epigenetic phenomena; RNA polymerase I; DNA methylation; cytosine methylation; histone methylation; histone deacetylation; histone deacetylase; transcription; ribosomal RNA; nucleolus; nucleolus organizer region Large scale cytological effects of rRNA gene regulation: nucleolus and secondary constriction formationThe most prominent feature of a eukaryotic nucleus during interphase is the nucleolus (Figure 1), a region that contains relatively little chromosomal DNA but is rich in RNAs, proteins and ribonucleoprotein particles, including the large and small ribosome subunits as they undergo assembly [1][2][3]. The location of a nucleolus is not determined randomly; instead its formation is determined by the position of a discrete chromosomal locus known as a nucleolus organizer region, or NOR [4]. This fact was discovered based on an intriguing property: upon condensation of chromosomes at metaphase, NORs fail to condense to the same extent as surrounding chromosomal sequences and thus give rise to "secondary constrictions", with "primary constrictions" being defined as the centromeres (see Figure 1). Heitz initially noted that nucleoli form at, or very near, the sites of secondary constrictions [5] and McClintock soon thereafter obtained direct evidence [6]. She identified a maize line in which a chromosome break at or near the secondary constriction on chromosome 9, followed by translocation of one *Author to whom correspondence should be addressed: pikaard@biology2.wustl.edu, phone: Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the conte...

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“…The nucleolus, whose function and components are known in detail, is the most well-characterized nuclear body and is exclusively reviewed elsewhere (e.g., Leung and Lamond 2003). The idea that other nuclear processes may occur in discrete sites within the nucleus owes an initial example to Hewson Swift (see Acknowledgments).…”

Section: Nuclear Bodiesmentioning

confidence: 99%

“…In many ways, the structure and function of cellular and subcellular organelles are inseparable; that is, disruptions in organelle function can lead to perturbations in its structure. Upon inhibition of rRNA transcription, for example, the nucleolus becomes disordered and ultimately disappears (Leung and Lamond 2003). This integration of structure and cellular function allows for conservation of resources and facilitates regulation at multiple levels.…”

mentioning

confidence: 99%

Form follows function: the genomic organization of cellular differentiation

Kosak¹,

Groudine²

2004

Genes Dev.

218

179

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The extent to which the nucleus is functionally organized has broad biological implications. Evidence supports the idea that basic nuclear functions, such as transcription, are structurally integrated within the nucleus. Moreover, recent studies indicate that the linear arrangement of genes within eukaryotic genomes is nonrandom. We suggest that determining the relationship between nuclear organization and the linear arrangement of genes will lead to a greater understanding of how transcriptomes, dedicated to a particular cellular function or fate, are coordinately regulated. Current network theories may provide a useful framework for modeling the inherent complexity the functional organization of the nucleus.Louis Sullivan, whose early efforts helped pioneer the development of the skyscraper, is considered one of the most important architects of the last century. However, it is his dictum-"form ever follows function"-for which he is perhaps best known. Just as this imperative has influenced generations of architects, the idea that structure reflects function provides a useful perspective for a biologist's view of the cell. In many ways, the structure and function of cellular and subcellular organelles are inseparable; that is, disruptions in organelle function can lead to perturbations in its structure. Upon inhibition of rRNA transcription, for example, the nucleolus becomes disordered and ultimately disappears (Leung and Lamond 2003). This integration of structure and cellular function allows for conservation of resources and facilitates regulation at multiple levels.Although a completely sequenced genome may represent a genetic blueprint, molecular biologists currently lack a key with which to fully grasp how this sequence is related to the development and subsequent maintenance of a given organism. Following Sullivan's example, a comprehensive understanding of genomic sequence may require considering its arrangement in the nucleus; the form DNA takes in the nucleus reveals not only its higher-order structure, but it may impart information regarding its function. The current paradigm of gene regulation includes the binding of site-specific transcription factors, the recruitment of cofactors and general transcription factors, and the incorporation of multiple modifications to both the DNA and the histones that organize it (Felsenfeld and Groudine 2003). This description of transcription belies its enormous complexity, fueled by an ever-increasing catalog of proteins dedicated in one way or another to its regulation. Additionally, evidence supporting the role of nuclear localization in transcriptional regulation indicates that it is insufficient to know the components of transcription . Rather, a thorough understanding of the process requires knowing its functional organization within the nucleus. In this sense, transcription should not be viewed simply as a process that turns on a specific gene, but as a process that governs within the genome an entire network of genes (a transcriptome) that gives rise to a p...

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The Dynamics of the Nucleolus

Cited by 83 publications

References 85 publications

Nucleolar stress is an early response to myocardial damage involving nucleolar proteins nucleostemin and nucleophosmin

Nucleolar stress is an early response to myocardial damage involving nucleolar proteins nucleostemin and nucleophosmin

rRNA gene silencing and nucleolar dominance: Insights into a chromosome-scale epigenetic on/off switch

Form follows function: the genomic organization of cellular differentiation

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