|
SUMMARY 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. KEY WORDS Nucleolus; cell cycle; dynamics; organization; nuclear domain; ribosome REFERENCES 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. Bell P., M.C. Dabauvalle, U. Scheer: In vitro assembly of prenucleolar bodies in Xenopus egg extract. J. Cell Biol. 118:1297-1304, 1992. 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. 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. 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. Carmo-Fonseca M., L. Mendes-Soares, I. Campos: To be or not to be in the nucleolus. Nature Cell Biol. 2:107-112, 2000. 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. 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. 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. Dundr M., T. Misteli, M.O.J. Olson: The dynamics of postmitotic reassembly of the nucleolus. J. Cell Biol. 150:433-446, 2000. 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. Fan H. and S. Penman: Regulation of synthesis and processing of nucleolar components in metaphase-arrested cells. J. Mol. Biol. 59:27-42, 1971. Fatica A. and D. Tollervey: Making ribosomes. Curr. Opin. Cell Biol. 14:313-318, 2002. 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. 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. 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. 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. Goessens G.: Nucleolar structure. Int. Rev. Cytol. 87:107-158, 1984. 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. 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. 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. 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. 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. 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. Hernandez-Verdun D., C.A. Bourgeois, M. Bouteille: Simultaneous nucleologenesis in daughter cells during late telophase. Bio Cell 37:1-4, 1980. Hozak P., J.T. Novak, K. Smetana: Threedimensional reconstructions of nucleolusorganizing regions in PHA-stimulated human lymphocytes. Biol. Cell 66:225-233, 1989. 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. 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. 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. 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. 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. 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. 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. Moyne G. and J. Garrido: Ultrastructural evidence of mitotic perichromosomal ribonucleoproteins in hamster cells. Exp. Cell Res. 98:237-247, 1976. 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. Olson M.O.J., M. Dundr, A. Szebeni: The nucleolus: an old factory with unexpected capabilities. Trends Cell Biol. 10:189-196, 2000. 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. Pederson T.: The plurifunctional nucleolus. Nucl. Acids Res. 26:3871-3876, 1998. Phair R.D., and T. Misteli: High mobility of proteins in the mammalian cell nucleus. Nature 404:604-609, 2000. Pinol-Roma S.: Association of nonribosomal nucleolar proteins in ribonucleoprotein complexes during interphase and mitosis. Mol. Biol. Cell 10:77-90, 1999. 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. Puvion-Dutilleul F., J.-P. Bachellerie, E. Puvion: Nucleolar organization of HeLa cells as studied by in situ hybridization. Chromosoma 100:395- 409, 1991. 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. 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. 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. Scheer U. and R. Benavente: Functional and dynamic aspects of the mammalian nucleolus. BioEssays 12:14-21, 1990. Scheer U. and R. Hock: Structure and function of the nucleolus. Curr. Opin. Cell Biol. 11:385- 390, 1999. 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-ß-Dribofuranosylbenzimidazole. J. Cell Biol. 99:672-679, 1984. 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. Shaw P.J. and E.G. Jordan: The nucleolus. Annu. Rev. Cell Dev. Biol. 11:93-121, 1995. 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. Sirri V., D. Hernandez-Verdun, P. Roussel: Cyclin-dependent kinases govern formation and maintenance of the nucleolus. J. Cell Biol. 156:969-981, 2002. 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. 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. 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. Thiry M. and G. Goessens: The nucleolus during the cell cycle. In Molecular Biology Intelligence Unit. Springer-Verlag, Heidelberg 1996. 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. 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. 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. 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. Visintin R. and A. Amon: The nucleolus: the magician's hat for cell cycle tricks. Curr. Opin. Cell Biol. 12:372-377, 2000. 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. |
CITED
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. |