Obsah souboru
<html>
<head>
<meta http-equiv="Content-Type" content="text/html; charset=windows-1250">
<meta name="Author" content="Josef Berger">
<title>Journal of Applied Biomedicine</title>
</head>
<body>
<style type="text/css">
documentByLine {display: none;}
</style>
<b><font color="#3366FF"><font size=+4>Journal of APPLIED BIOMEDICINE</font></font></b><br>
ISSN 1214-0287 (on-line)<br>
ISSN 1214-021X (printed)
<br><br>
Volume 2 (2004), No 2, p 57-69
<br><br>
<hr WIDTH="100%">
<br><br>
<font size=+2><b>
The nucleolus: functional organization and assembly
</b></font>
<br><br>
<i>
Daniele Hernandez-Verdun
</i>
<br><br>
Address: Daniele Hernandez-Verdun, Institut Jacques Monod, 2 place Jussieu, 75251 Paris Cedex 05, France
<br><br>
Received 23rd May, 2003.<br>
Published online 4th July, 2003.<br>
<br>
<a href="http://www.zsf.jcu.cz/jab/2_2/hernandez.pdf">Full text article (pdf)</a><br>
<a href="http://www.zsf.jcu.cz/jab/2_2/hernandez.html">Full text article (html)</a><br>
<br>
<table cellspacing=2>
<tr>
<td width=80% valign=top align=left>
<a name="summary"><b>SUMMARY</b></a><br>
The nucleolus is a large nuclear domain generated by the act of building ribosomes. It illustrates the compartmentation of the nuclear functions, since it is in the nucleolus that transcription of the ribosomal genes, maturation and processing of the 47S ribosomal RNAs (rRNAs) into 18S, 5.8S and
28S rRNA, and almost complete assembly of the 40S and 60S ribosome subunits take place. The shape, size and organization of the nucleoli vary with their activity. Nuleolar activity is a cell cycle dependent-process. In electron microscopy, the nucleolus exhibits three main components: fibrillar
centers (FCs), a dense fibrillar component (DFC) and a granular component (GC), corresponding to different steps of ribosome biogenesis. The steady state between transcription, processing and export of ribosomal subunits engenders this organization. Conversely, inactivation or blockage of one of
these processes modifies the organization of the nucleolus and ultimately induces nucleolar disassembly. The nucleolus is also a plurifunctional domain, a key partner of chromatin architecture in the nucleus and it plays a crucial role in several cellular functions in addition to ribosome
production.
The nucleolus is assembled at the end of mitosis, is active during interphase, and disassembled in prophase. The nucleolar transcription and processing machineries are inherited from parental to daughter cells through mitosis. The polymerase I (pol I) transcription machinery is repressed during mitosis although assembled with ribosomal genes. Repression of pol I transcription is achieved at the end of prophase and is maintained during mitosis through phosphorylation of transcription factors by the cyclin-dependent kinase (CDK) 1. The nucleolar processing machineries relocalize
from the nucleolus towards the periphery of all chromosomes until telophase and this chromosome association depends on CDK1 activity. As a consequence of natural inhibition of CDK1 activity, pol I transcription is restored in telophase. The processing machineries are recruited to the sites of
rDNA transcription after a temporary transit in foci known as prenucleolar bodies. In conclusion, the behavior of the nucleolus illustrates the fact that the dynamics of nuclear organization are integrated in a network of interactions and controls that is largely dependent on the coordination of cell cycle controls.
<br><br>
<a name="keywords"><b>KEY WORDS</b></a><br>
Nucleolus; cell cycle; dynamics; organization; nuclear domain; ribosome<br>
<br><br>
<a name="references"><b>REFERENCES</b></a><br>
Andersen J.S., C.E. Lyon, A.H. Fox, A.K.L. Leung, Y.W. Lam, H. Steen, M. Mann, A. I. Lamond: Directed proteomic analysis of the human nucleolus. Curr. Biol. 12:1-11, 2002.<br><br>
Bell P., M.C. Dabauvalle, U. Scheer: In vitro assembly of prenucleolar bodies in Xenopus egg extract. J. Cell Biol. 118:1297-1304, 1992.<br><br>
Beven A.F., R. Lee, M. Razaz, D.J. Leader, J.W.S. Brown, P.J. Shaw: The organization of ribosomal RNA processing correlates with the distribution of nucleolar snRNAs. J. Cell Sci. 109:1241-1251, 1996.<br><br>
Biggiogera M., M. Malatesta, S. Abolhassani-Dadras, F. Amalric, L.I. Rothblum, S. Fakan: Revealing the unseen: the organizer of the nucleolus. J. Cell Sci. 17:3199-3205, 2001.<br><br>
Busch H. and K. Smetana: The nucleus of cancer cells. In H. Busch (ed), The Molecular Biology of Cancer. Academic Press, New York 1974, pp. 41-80.<br><br>
Carmo-Fonseca M., L. Mendes-Soares, I. Campos: To be or not to be in the nucleolus. Nature Cell Biol. 2:107-112, 2000.<br><br>
Chubb J.R., S. Boyle, P. Perry, W.A. Bickmore: Chromatin motion is constrained by association with nuclear compartments in human cells. Curr. Biol. 12:439-445, 2002.<br><br>
Cmarko D., P.J. Verschure, L.I. Rothblum, D. Hernandez-Verdun, F. Amalric, R. van Driel, S. Fakan: Ultrastructural analysis of nucleolar transcription in cells microinjected with 5-bromo-UTP. Histochem. Cell Biol. 113:181-187, 2000.<br><br>
Dousset T., C. Wang, C. Verheggen, D. Chen, D. Hernandez-Verdun, S. Huang: Initiation of nucleolar assembly is independent of RNA polymerase I transcription. Mol. Biol. Cell 11:2705-2717, 2000.<br><br>
Dundr M., T. Misteli, M.O.J. Olson: The dynamics of postmitotic reassembly of the nucleolus. J. Cell Biol. 150:433-446, 2000.<br><br>
Dundr M. and M.O.J. Olson: Partially processed pre-rRNA is preserved in association with processing components in nucleolus derived foci during mitosis. Mol. Biol. Cell 9:2407-2422, 1998.<br><br>
Fan H. and S. Penman: Regulation of synthesis and processing of nucleolar components in metaphase-arrested cells. J. Mol. Biol. 59:27-42, 1971.<br><br>
Fatica A. and D. Tollervey: Making ribosomes. Curr. Opin. Cell Biol. 14:313-318, 2002.<br><br>
Fomproix N., J. Gebrane-Younes, D. Hernandez-Verdun: Effects of anti-fibrillarin antibodies on building of functional nucleoli at the end of mitosis. J. Cell Sci. 111:359-372, 1998.<br><br>
Gautier T., N. Fomproix, C. Masson, M.C. Azum-Gelade, N. Gas, D. Hernandez-Verdun: Fate of specific nucleolar perichromosomal proteins during mitosis: Cellular distribution and association with U3 snoRNA. Biol. Cell 82:81-93, 1994.<br><br>
Gebrane-Younes J., N. Fomproix, D. Hernandez-Verdun: When rDNA transcription is arrested during mitosis, UBF is still associated with noncondensed
rDNA. J. Cell Sci. 110:2429-2440, 1997.<br><br>
Gerlich D., J. Beaudouin, B. Kalbfuss, N. Daigle, R. Eils, J. Ellenberg: Global chromosome positions are transmitted through mitosis in mammalian cells. Cell 112:751, 2003.<br><br>
Goessens G.: Nucleolar structure. Int. Rev. Cytol. 87:107-158, 1984.<br><br>
Granick D.: Nucleolar necklaces in chick embryo fibroblast cells. I. Formation of necklaces by dichlororibobenzimidazole and other adenosine analogues that decrease RNA synthesis and degrade preribosomes. J. Cell Biol. 65:398-417, 1975a.<br><br>
Granick D.: Nucleolar necklaces in chick embryo fibroblast cells. II. Microscope observations of the effect of adenosine analogues on nucleolar necklace formation. J. Cell Biol. 65:418-427, 1975b.<br><br>
Haaf T. and D.C. Ward: Inhibition of RNA polymerase II transcription causes chromatin decondensation, loss of nucleolar structure, and dispersion of chromosomal domains. Exp. Cell Res. 224:163-173, 1996.<br><br>
Hadjiolov A.A.: The nucleolus and ribosome biogenesis. In M. Alfert, W. Beermann, L. Goldstein, K.R. Porter, P. Sitte, (eds) : Cell Biology Monographs, Vol. 12, Springer-Verlag, Wien 1985.<br><br>
Harnpicharnchai P., J. Jakovljevic, E. Horsey, T. Miles, J. Roman, M. Rout, D. Meagher, B. Imai, Y. Guo, C.J. Brame, J. Shabanowitz, D.F. Hunt, J.L. Woolford: Composition and functional characterization of yeast 66S ribosome assembly intermediates. Mol. Cell 8:505-515, 2001.<br><br>
Heix J., A. Vente, R. Voit, A. Budde, T.M. Michaelidis, I. Grummt: Mitotic silencing of human rRNA synthesis: inactivation of the promoter selectivity factor SL1 by cdc2/cyclin B-mediated phosphorylation. EMBO J. 17:7373-7381, 1998.<br><br>
Hernandez-Verdun D., C.A. Bourgeois, M. Bouteille: Simultaneous nucleologenesis in daughter cells during late telophase. Bio Cell 37:1-4, 1980.<br><br>
Hozak P., J.T. Novak, K. Smetana: Threedimensional reconstructions of nucleolusorganizing regions in PHA-stimulated human lymphocytes. Biol. Cell 66:225-233, 1989.<br><br>
Jimenez-Garcia L.F., M. de L. Segura-Valdez, R.L Ochs, L.I. Rothblum, R. Hannan, D.L. Spector: Nucleologenesis: U3 snRNAcontaining prenucleolar bodies move to sites of active pre-rRNA transcription after mitosis. Mol. Biol. Cell 5:955-966, 1994.<br><br>
Junera H. R., C. Masson, G. Geraud, D. Hernandez-
Verdun: The three-dimensional organization of
ribosomal genes and the architecture of the
nucleoli vary with G1, S and G2 phases. J. Cell
Sci. 108:3427-3441, 1995.<br><br>
Junera H.R., C. Masson, G. Geraud, J. Suja,
D. Hernandez-Verdun: Involvement of in situ
conformation of ribosomal genes and selective
distribution of UBF in rRNA transcription. Mol.
Biol. Cell 8:145-156, 1997.<br><br>
Le Panse S., C. Masson, L. Heliot, J.-M. Chassery,
H. R. Junera, D. Hernandez-Verdun: 3-D
organization of single ribosomal transcription
units after DRB inhibition of RNA polymerase II
transcription. J. Cell Sci. 112:2145-2154, 1999.<br><br>
Leung A.K.L. and A.I. Lamond: In vivo analysis of
NHPX reveals a novel nucleolar localization
pathway involving a transient accumulation in
splicing speckles. J. Cell Biol. 157:615-629,
2002.<br><br>
McClintock B.: The relation of particular
chromosomal element to the development of the
nucleoli in Zea mays. Z. Zellforsch. mikrosk.
Anat. 21:294-328, 1934.<br><br>
Melese T. and Z. Xue: The nucleolus: an organelle
formed by ,the act of buiding a ribosome. Curr.
Opin. Cell Biol. 7: 319-324, 1995.
Misteli T.: Protein dynamics: implications for
nuclear architecture and gene expression.
Science 291:843-847, 2001.<br><br>
Moyne G. and J. Garrido: Ultrastructural evidence
of mitotic perichromosomal ribonucleoproteins
in hamster cells. Exp. Cell Res. 98:237-247,
1976.<br><br>
Nissan T.A., J. Bassler, E. Petfalski, D. Tollervey,
E. Hurt: 60S pre-ribosome formation viewed
from assembly in the nucleolus until export to
the cytoplasm. EMBO J. 21:5539-5547, 2002.<br><br>
Olson M.O.J., M. Dundr, A. Szebeni: The
nucleolus: an old factory with unexpected
capabilities. Trends Cell Biol. 10:189-196,
2000.<br><br>
Pebusque M.J. and R. Seite: Electron microscopic
studies of silver-stained proteins in nucleolar
organizer regions: location in nucleoli of rat
sympathetic neurons during light and dark
periods. J. Cell Sci. 51:85-94, 1981.<br><br>
Pederson T.: The plurifunctional nucleolus. Nucl.
Acids Res. 26:3871-3876, 1998.<br><br>
Phair R.D., and T. Misteli: High mobility of
proteins in the mammalian cell nucleus. Nature
404:604-609, 2000.<br><br>
Pinol-Roma S.: Association of nonribosomal
nucleolar proteins in ribonucleoprotein
complexes during interphase and mitosis. Mol.
Biol. Cell 10:77-90, 1999.<br><br>
Prescott D.M. and M.A. Bender: Synthesis of RNA
and protein during mitosis in mammalian tissue
culture cells. Exp. Cell Res. 26:260-268, 1962.<br><br>
Puvion-Dutilleul F., J.-P. Bachellerie, E. Puvion: Nucleolar organization of HeLa cells as studied
by in situ hybridization. Chromosoma 100:395-
409, 1991.<br><br>
Puvion-Dutilleul F., E. Puvion, J.-P. Bachellerie:
Early stages of pre-rRNA formation within the
nucleolar ultrastructure of mouse cells studied by
in situ hybridization with 5'ETS leader probe.
Chromosoma 105:496-505, 1997.<br><br>
Roussel P., C. Andre, L. Comai, D. Hernandez-
Verdun: The rDNA transcription machinery is
assembled during mitosis in active NORs and
absent in inactive NORs. J. Cell Biol. 133:235-
246, 1996.<br><br>
Savino T.M., J. Gebrane-Younes, J. De Mey,
J.-B. Sibarita, D. Hernandez-Verdun: Nucleolar
assembly of the rRNA processing machinery in
living cells. J. Cell Biol. 153:1097-1110, 2001.<br><br>
Scheer U. and R. Benavente: Functional and
dynamic aspects of the mammalian nucleolus.
BioEssays 12:14-21, 1990.<br><br>
Scheer U. and R. Hock: Structure and function of
the nucleolus. Curr. Opin. Cell Biol. 11:385-
390, 1999.<br><br>
Scheer U., B. Hugle, R. Hazan, K.M. Rose: Druginduced
dispersal of transcribed rRNA genes and
transcriptional products: immunolocalization and
silver staining of different nucleolar components
in rat cells treated with 5,6-dichloro-�-Dribofuranosylbenzimidazole.
J. Cell Biol. 99:672-679, 1984.<br><br>
Scherl A., Y. Coute, C. Deon, A. Calle,
K. Kindbeiter, J.-C.Sanchez, A. Greco,
D. Hochstrasser, J.-J. Diaz: Functional proteomic
analysis of human nucleolus. Molec. Biol. Cell
13:4100-4109, 2002.<br><br>
Shaw P.J. and E.G. Jordan: The nucleolus. Annu.
Rev. Cell Dev. Biol. 11:93-121, 1995.<br><br>
Shou W., K.M. Sakamoto, J. Keener,
K.W. Morimoto, E.E.Traverso, R. Azzam,
G.J. Hoppe, R.M. Feldman, J.DeModena,
D. Moazed, H. Charbonneau, M. Nomura,
R.J. Deshaies: Net1 stimulates RNA
polymerase I transcription and regulates
nucleolar structure independently of controlling
mitotic exit. Mol. Cell 8:45-55, 2001.<br><br>
Sirri V., D. Hernandez-Verdun, P. Roussel:
Cyclin-dependent kinases govern formation and
maintenance of the nucleolus. J. Cell Biol. 156:969-981, 2002.<br><br>
Sirri V., P. Roussel, D. Hernandez-Verdun: The
mitotically phosphorylated form of the transcription termination factor TTF-1 is
associated with the repressed rDNA transcription
machinery. J. Cell Sci. 112:3259-3268, 1999.<br><br>
Sirri V., P. Roussel, D. Hernandez-Verdun: In vivo
release of mitotic silencing of ribosomal gene
transcription does not give rise to precursor
ribosomal RNA processing. J. Cell Biol. 148:259-270, 2000.<br><br>
Snaar S., K. Wiesmeijer, A.G. Jochemsen,
H.J. Tanke, R.W.Dirks: Mutational analysis of
fibrillarin and its mobility in living human cells.
J. Cell Biol. 151:653-662, 2000.<br><br>
Thiry M. and G. Goessens: The nucleolus during the
cell cycle. In Molecular Biology Intelligence
Unit. Springer-Verlag, Heidelberg 1996.<br><br>
Thiry M. and L. Thiry-Blaise: Locating transcribed
and non-transcribed rDNA spacer sequences
within the nucleolus by in situ hybridization and
immunoelectron microscopy. Nucleic Acids. Res.
19:11-15, 1991.<br><br>
Trumtel S., I. Leger-Silvestre, P.-E. Gleizes,
F. Teulieres, N. Gas: Assembly and functional
organization of the nucleolus: ultrastructural
analysis of Saccharomyces cerevisiae mutants.
Mol. Biol. Cell 11:2175-2189, 2000.<br><br>
Tsai R.Y.L. and R.D.G. McKay: A nucleolar
mechanism controlling cell proliferation in stem
cells and cancer cells. Genes dev. 16:2991-
3003, 2002.<br><br>
Verheggen C., G. Almouzni, and D. Hernandez-
Verdun: The ribosomal RNA processing
machinery is recruited to the nucleolar domain
before RNA polymerase I during Xenopus laevis
development. J. Cell Biol. 149:293-305, 2000.<br><br>
Visintin R. and A. Amon: The nucleolus: the
magician's hat for cell cycle tricks. Curr. Opin.
Cell Biol. 12:372-377, 2000.<br><br>
Weisenberger D. and U. Scheer: A possible
mechanism for the inhibition of ribosomal RNA
gene transcription during mitosis. J. Cell Biol.
129:561-575, 1995.
<br>
</td>
<td valign=top align=left bgcolor=silver>
<a name="cited"><b>CITED</b></a>
<br><br>
<small>
Berger J, Machackova M, Berger Z: Effects of feed restriction on the nucleolar structure and function in lymphocytes.
Basic Clin Pharmacol Toxicol 97:236-237.
</small>
</td>
</tr>
</table>
<br>
<a href="http://www.zsf.jcu.cz/jab">BACK</a>
</body>
</html>
hernandez-old.htm