WordNet

small room in which a monk or nun lives (同)cubicle
a device that delivers an electric current as the result of a chemical reaction (同)electric cell
a room where a prisoner is kept (同)jail cell, prison cell
(biology) the basic structural and functional unit of all organisms; they may exist as independent units of life (as in monads) or may form colonies or tissues as in higher plants and animals
any small compartment; "the cells of a honeycomb"
a small unit serving as part of or as the nucleus of a larger political movement (同)cadre
a small round body of protein in a cell nucleus; such organelles contain RNA and are involved in protein synthesis (同)nucleole

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(刑務所の)『独房』;(修道院の)小さい独居室 / (ミツバチの)みつ房,巣穴 / 小さい部屋 / 『細胞』 / 電池 / 花粉室 / (共産党などの)細胞
(細胞核内の)小核,核仁

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/08/07 16:30:31」(JST)

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The nucleolus is contained within the cell nucleus.

Schematic of typical animal cell, showing subcellular components. Organelles:
(1) Nucleolus
(2) Nucleus
(3) Ribosomes (little dots)
(4) Vesicle
(5) Rough endoplasmic reticulum (ER)
(6) Golgi apparatus
(7) Cytoskeleton
(8) Smooth ER
(9) Mitochondria
(10) Vacuole
(11) Cytosol
(12) Lysosome

(13) Centrioles within Centrosome

The nucleolus (plural nucleoli) is a non-membrane bound structure^[1] composed of proteins and nucleic acids found within the nucleus of cells. Ribosomal RNA (rRNA) is transcribed and assembled within the nucleolus. The nucleolus ultrastructure can be visualized through an electron microscope, while the organization and dynamics can be studied through fluorescent protein tagging and fluorescent recovery after photobleaching (FRAP). Malfunction of nucleoli can be the cause for several human diseases. It takes up to about 25% of the nuclear volume.

Structure

Three major components of the nucleolus are recognized: the fibrillar centers (FC), the dense fibrillar components (DFC), and granular components (GC).^[2] The DFC or pars fibrosa consists of newly transcribed rRNA bound to ribosomal proteins, while the GC, called pars granulosa, contains rRNA bound to ribosomal proteins that are beginning to assemble into ribosomes. However, it has been proposed that this particular organization is only observed in higher eukaryotes and that it evolved from a bipartite organization with the transition from anamniotes to amniotes. Reflecting the substantial increase in the DNA intergenic region, an original fibrillar component would have separated into the FC and the DFC.^[3] Another structure identified within many nucleoli (particularly in plants) is a clear area in the center of the structure referred to as a nucleolar vacuole.^[4]

Function and ribosome assembly

Photomicrograph of nucleus and nucleolus

Nucleoli are formed around specific genetic loci called nucleolar organizing regions (NORs), first described by Barbara McClintock. Because of this non-random organization, the nucleolus is defined as a "genetically determined element."^[5] A NOR is composed of tandem repeats of rRNA genes, which can be found in several different chromosomes. The human genome, for example, contains more than 200 clustered copies of the rRNA genes on five different chromosomes (13, 14, 15, 21, 22). In a typical eukaryote, a rRNA gene consists of a promoter, internal and external transcribed spacers (ITS/ETS), rRNA coding sequences (18S, 5.8S, 28S) and an external non-transcribed spacer.^[6] In ribosome biogenesis, two of the three eukaryotic RNA polymerases (pol I and III) are required, and these function in a coordinated manner. In an initial stage, the rRNA genes are transcribed as a single unit within the nucleolus by RNA pol I or III. In order for this transcription to occur, several pol I-associated factors and DNA-specific transacting factors are required. In yeast, the most important are: UAF (upstream activating factor), TBP (tata-box binding protein), and CF (core factor), which bind promoter elements and form the preinitiation complex (PIC), which is in turn recognized by RNA pol. In humans, a similar PIC is assembled with SLI, the promoter selectivity factor (composed of TBP and TBP-associated factors, or TAFs), IFs (transcription initiation factors) and UBF (upstream binding factor). RNA polymerase I transcribes most rRNA transcripts (28S, 18S, and 5.8S) but the 5S rRNA subunit (component of the 60S ribosomal subunit) is transcribed by RNA polymerase III.^[7]

Transcription of the ribosomal gene yields a long precursor molecule (45S pre-rRNA) which still contains the ITS and ETS. Further processing is needed to generate the 18S RNA, 5.8S and 28S RNA molecules. In eukaryotes, the RNA-modifying enzymes are brought to their respective recognition sites by interaction with guide RNAs, which bind these specific sequences. These guide RNAs belong to the class of small nucleolar RNAs (snoRNAs) which are complexed with proteins and exist as small-nucleolar-ribonucleoproteins (snoRNPs). Once the rRNA subunits are processed, they are ready to be assembled into larger ribosomal subunits. However, an additional rRNA molecule, the 5S rRNA, is also necessary. In yeast, the 5S rDNA sequence is localized in the external non-transcribed spacer and is transcribed in the nucleolus by RNA pol. In higher eukaryotes and plants, the situation is more complex, for the 5S DNA sequence lies outside the NOR and is transcribed by RNA pol III in the nucleoplasm, after which it finds its way into the nucleolus to participate in the ribosome assembly. This assembly not only involves the rRNA, but ribosomal proteins as well. The genes encoding these r-proteins are transcribed by pol II in the nucleoplasm by a "conventional" pathway of protein synthesis (transcription, pre-mRNA processing, nuclear export of mature mRNA and translation on cytoplasmic ribosomes). The mature r-proteins are then "imported" back into the nucleus and finally the nucleolus. Association and maturation of rRNA and r-proteins result in the formation of the 40S (small) and 60S (large) subunits of the complete ribosome. These are exported through the nuclear pore complexes to the cytoplasm, where they remain free or become associated with the endoplasmic reticulum, forming rough endoplasmic reticulum (RER).^[6]^[8]

A continuous chain between the nucleoplasm and the inner parts of the nucleolus exists through a network of nucleolar channels. In this way, macromolecules with a molecular weight up to 2000 kDa are easily distributed throughout the nucleolus.^{[citation needed]}

Sequestration of proteins

In addition to its role in ribosomal biogenesis, the nucleolus is known to capture and immobilize proteins, a process known as nucleolar sequestration. Proteins that are sequestered in the nucleolus are unable to diffuse and to interact with their binding partners. Targets of this post-translational regulatory mechanism include VHL, PML, MDM2, RelA, HAND1 and hTERT, among many others. It is now known that noncoding RNAs originating from intergenic regions of the nucleolus are responsible for this phenomenon^[9].

Notes

^ http://micro.magnet.fsu.edu/cells/nucleus/nucleolus.html
^ Koberna K, Malínský J, Pliss A, et al. (May 2002). "Ribosomal genes in focus: new transcripts label the dense fibrillar components and form clusters indicative of "Christmas trees" in situ". J. Cell Biol. 157 (5): 743–8. doi:10.1083/jcb.200202007. PMC CHEESE 423/?tool=pmcentrez 2173 CHEESE 423. PMID 12034768. http://www.jcb.org/cgi/pmidlookup?view=long&pmid=12034768.
^ 7. Thiry, M., Lafontaine, L. J. (2005) Birth of a nucleolus: the evolution of nucleolar compartments. TRENDS in Cell Biology 15 [1]
^ Beven AF, Lee R, Razaz M, Leader DJ, Brown JW, Shaw PJ (1 June 1996). "The organization of ribosomal RNA processing correlates with the distribution of nucleolar snRNAs". J. Cell. Sci. 109 (6): 1241–51. PMID 8799814. http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=8799814.
^ Raška, I. Shaw, P. J., Cmarko, D. (2006) New Insights into Nucleolar Architecture and Activity [2]
^ ^a ^b Bruce Alberts, et al. (2002) The Molecular Biology of the Cell (4th edition). Garland Science 331–333
^ Champe, P; Lippincott's Illustrated Reviews: Biochemistry.
^ Geoffrey M. Cooper, Robert E. Hausman. The Cell, A Molecular Approach (4th edition). Sinauer Associates 371–379
^ Audas TE, Jacob MD, Lee S. (January 2012). "Immobilization of proteins in the nucleolus by ribosomal intergenic spacer noncoding RNA". Mol Cell. 157 (45(2)): 147-57. doi:10.1016/j.molcel.2011.12.012. PMID 22284675. http://www.cell.com/molecular-cell/abstract/S1097-2765%2811%2900954-3.

External links

Nucleolus under electron microscope II at uni-mainz.de
Nuclear Protein Database - search under compartment
Cell+Nucleolus at the US National Library of Medicine Medical Subject Headings (MeSH)
BU Histology Learning System: 20104loa

UpToDate Contents

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English Journal

macroH2A1 histone variant represses rDNA transcription.

Cong R, Das S, Douet J, Wong J, Buschbeck M, Mongelard F, Bouvet P.Author information Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS USR 3010, Laboratoire Joliot-Curie, 69364 Lyon, France, The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), 08916 Badalona, Barcelona, Spain and The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.AbstractThe regulation of ribosomal DNA transcription is an important step for the control of cell growth. Epigenetic marks such as DNA methylation and posttranslational modifications of canonical histones have been involved in this regulation, but much less is known about the role of histone variants. In this work, we show that the histone variant macroH2A1 is present on the promoter of methylated rDNA genes. The inhibition of the expression of macroH2A1 in human HeLa and HepG2 cells and in a mouse ES cell line resulted in an up to 5-fold increase of pre-rRNA levels. This increased accumulation of pre-rRNA is accompanied by an increase of the loading of RNA polymerase I and UBF on the rDNA without any changes in the number of active rDNA genes. The inhibition of RNA polymerase I transcription by actinomycin D or by knocking down nucleolin, induces the recruitment of macroH2A1 on the rDNA and the relocalization of macroH2A1 in the nucleolus. Interestingly, the inhibition of rDNA transcription induced by nucleolin depletion is alleviated by the inactivation of macroH2A1. These results demonstrate that macroH2A1 is a new factor involved in the regulation of rDNA transcription.
Nucleic acids research.Nucleic Acids Res.2014 Jan 7;42(1):181-92. doi: 10.1093/nar/gkt863. Epub 2013 Sep 25.
The regulation of ribosomal DNA transcription is an important step for the control of cell growth. Epigenetic marks such as DNA methylation and posttranslational modifications of canonical histones have been involved in this regulation, but much less is known about the role of histone variants. In t
PMID 24071584

Neurodegeneration-associated instability of ribosomal DNA.

Hallgren J1, Pietrzak M1, Rempala G2, Nelson PT3, Hetman M4.Author information 1Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY 40292, USA; Department of Neurological Surgery, University of Louisville, Louisville, KY 40292, USA.2Division of Biostatistics, College of Public Health, Ohio State University, Columbus, OH 43210, USA.3Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536-0230, USA.4Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY 40292, USA; Department of Neurological Surgery, University of Louisville, Louisville, KY 40292, USA; Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY 40292, USA. Electronic address: michal.hetman@louisville.edu.AbstractHomologous recombination (HR)-mediated instability of the repetitively organized ribosomal DNA (rDNA) has been proposed as a mediator of cell senescence in yeast triggering the DNA damage response. High individual variability in the content of human rDNA suggests that this genomic region remained relatively unstable throughout evolution. Therefore, quantitative real-time polymerase chain reaction was used to determine the genomic content of rDNA in post mortem samples of parietal cortex from 14 young and 9 elderly individuals with no diagnosis of a chronic neurodegenerative/neurological disease. In addition, rDNA content in that brain region was compared between 10 age-matched control individuals and 10 patients with dementia with Lewy bodies (DLB) which involves neurodegeneration of the cerebral cortex. Probing rRNA-coding regions of rDNA revealed no effects of aging on the rDNA content. Elevated rDNA content was observed in DLB. Conversely, in the DLB pathology-free cerebellum, lower genomic content of rDNA was present in the DLB group. In the parietal cortex, such a DLB-associated instability of rDNA was not accompanied by any major changes of cytosine-phosphate-guanine methylation of the rDNA promoter. As increased cerebro-cortical rDNA content was previously reported in Alzheimer's disease, neurodegeneration appears to be associated with instability of rDNA. The hypothetical origins and consequences of this phenomenon are discussed including possibilities that the DNA damage-induced recombination destabilizes rDNA and that differential content of rDNA affects heterochromatin formation, gene expression and/or DNA damage response. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease.
Biochimica et biophysica acta.Biochim Biophys Acta.2014 Jan 2. pii: S0925-4439(13)00375-X. doi: 10.1016/j.bbadis.2013.12.012. [Epub ahead of print]
Homologous recombination (HR)-mediated instability of the repetitively organized ribosomal DNA (rDNA) has been proposed as a mediator of cell senescence in yeast triggering the DNA damage response. High individual variability in the content of human rDNA suggests that this genomic region remained re
PMID 24389328

Coupled GTPase and remodelling ATPase activities form a checkpoint for ribosome export.

Matsuo Y1, Granneman S2, Thoms M3, Manikas RG1, Tollervey D4, Hurt E1.Author information 1Biochemie-Zentrum der Universität Heidelberg, Im Neuenheimer Feld 328, Heidelberg D-69120, Germany.21] Wellcome Trust Centre for Cell Biology, The University of Edinburgh, Edinburgh EH9 3JR, UK [2] Centre for Synthetic and Systems Biology, The University of Edinburgh, Edinburgh EH9 3JD, UK [3].31] Biochemie-Zentrum der Universität Heidelberg, Im Neuenheimer Feld 328, Heidelberg D-69120, Germany [2].4Wellcome Trust Centre for Cell Biology, The University of Edinburgh, Edinburgh EH9 3JR, UK.AbstractEukaryotic ribosomes are assembled by a complex pathway that extends from the nucleolus to the cytoplasm and is powered by many energy-consuming enzymes. Nuclear export is a key, irreversible step in pre-ribosome maturation, but mechanisms underlying the timely acquisition of export competence remain poorly understood. Here we show that a conserved Saccharomyces cerevisiae GTPase Nug2 (also known as Nog2, and as NGP-1, GNL2 or nucleostemin 2 in human) has a key role in the timing of export competence. Nug2 binds the inter-subunit face of maturing, nucleoplasmic pre-60S particles, and the location clashes with the position of Nmd3, a key pre-60S export adaptor. Nug2 and Nmd3 are not present on the same pre-60S particles, with Nug2 binding before Nmd3. Depletion of Nug2 causes premature Nmd3 binding to the pre-60S particles, whereas mutations in the G-domain of Nug2 block Nmd3 recruitment, resulting in severe 60S export defects. Two pre-60S remodelling factors, the Rea1 ATPase and its co-substrate Rsa4, are present on Nug2-associated particles, and both show synthetic lethal interactions with nug2 mutants. Release of Nug2 from pre-60S particles requires both its K(+)-dependent GTPase activity and the remodelling ATPase activity of Rea1. We conclude that Nug2 is a regulatory GTPase that monitors pre-60S maturation, with release from its placeholder site linked to recruitment of the nuclear export machinery.
Nature.Nature.2014 Jan 2;505(7481):112-6. doi: 10.1038/nature12731. Epub 2013 Nov 17.
Eukaryotic ribosomes are assembled by a complex pathway that extends from the nucleolus to the cytoplasm and is powered by many energy-consuming enzymes. Nuclear export is a key, irreversible step in pre-ribosome maturation, but mechanisms underlying the timely acquisition of export competence remai
PMID 24240281

Japanese Journal

Blastic Plasmacytoid Dendritic Cell Neoplasm : Report of Two Cases

TSUNODA Kanako,SATOH Takashi,AKASAKA Kiyomi,ISHIKAWA Yuichi,ISHIDA Yoji,MASUDA Tomoyuki,AKASAKA Toshihide
Journal of clinical and experimental hematopathology 52(1), 23-29, 2012-05-01
… Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a clinically aggressive tumor derived from the precursor of plasmacytoid dendritic cells. … Histopathology of a skin biopsy specimen and immunohistochemistry demonstrated that the tumor cells were small to medium-sized with a blastoid morphology and positive for CD4, CD56, CD123 and T-cell leukemia-1 (TCL-1). …
NAID 10030615559

Location of rRNA Transcription to the Nucleolar Components : Disappearance of the Fibrillar Centers in Nucleoli of Regenerating Rat Hepatocytes

Montanaro Lorenzo,Govoni Marzia,Orrico Catia [他]
Cell
NAID 40019163882

Drosophila GTPase Nucleostemin 2 Changes Cellular Distribution during Larval Development and the GTP-Binding Motif Is Essential to Nucleoplasmic Localization

Matsuo Eriko,Nagamine Toshihiro,Matsumoto Shogo [他],TSUNEIZUMI Kazuhide
Bioscience, biotechnology, and biochemistry 75(8), 1511-1515, 2011-08-23
… Nucleostemin (NS), a nucleolar guanosine triphosphate (GTP)-binding protein, plays significant roles in cell cycle progression and ribosomal biogenesis. … NS family, regulates early eye development and is essential to cell survival <I>in vivo</I>, but the underlying mechanisms have yet to be clarified. …
NAID 10029591473