In higher eukaryotic cells, the nucleolus is a nuclear compartment assembled at the beginning of interphase, maintained during interphase, and disorganized during mitosis. Even if its structural organization appears to be undissociable from its function in ribosome biogenesis, the mechanisms that govern the formation and maintenance of the nucleolus are not elucidated. To determine if cell cycle regulators are implicated, we investigated the putative role of the cyclin-dependent kinases (CDKs) on ribosome biogenesis and nucleolar organization. Inhibition of CDK1–cyclin B during mitosis leads to resumption of rDNA transcription, but is not sufficient to induce proper processing of the pre-rRNA and total relocalization of the processing machinery into rDNA transcription sites. Similarly, at the exit from mitosis, both translocation of the late processing machinery and pre-rRNA processing are impaired in a reversible manner by CDK inhibitors. Therefore, CDK activity seems indispensable for the building of functional nucleoli. Furthermore, inhibition of CDKs in interphasic cells also hampered proper pre-rRNA processing and induced a dramatic disorganization of the nucleolus. Thus, we propose that the mechanisms governing both formation and maintenance of functional nucleoli involve CDK activities and couple the cell cycle to ribosome biogenesis.
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18 March 2002
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March 18 2002
Cyclin-dependent kinases govern formation and maintenance of the nucleolus
Valentina Sirri,
Valentina Sirri
Institut Jacques Monod, UMR 7592, 75251 Paris, France
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Danièle Hernandez-Verdun,
Danièle Hernandez-Verdun
Institut Jacques Monod, UMR 7592, 75251 Paris, France
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Pascal Roussel
Pascal Roussel
Institut Jacques Monod, UMR 7592, 75251 Paris, France
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Valentina Sirri
Institut Jacques Monod, UMR 7592, 75251 Paris, France
Danièle Hernandez-Verdun
Institut Jacques Monod, UMR 7592, 75251 Paris, France
Pascal Roussel
Institut Jacques Monod, UMR 7592, 75251 Paris, France
Address correspondence to D. Hernandez-Verdun, Institut Jacques Monod, 2 place Jussieu, 75251 Paris Cedex 05, France. Tel.: 33-1-4427-4038. Fax: 33-1-4427-5994. E-mail: [email protected]
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Abbreviations used in this paper: CDK, cyclin-dependent kinase; DFC, dense fibrillar component; ERK, extracellular signal-regulated kinase; ETS, external transcribed spacer; FC, fibrillar center; GC, granular component; GFP, green fluorescent protein; NOR, nucleolar organizer region; nt, nucleotide; PNB, prenucleolar body; pol, RNA polymerase; RT, room temperature; snoRNA, small nucleolar RNA; UBF, upstream binding factor.
Received:
January 04 2002
Revision Received:
January 29 2002
Accepted:
January 29 2002
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2002
J Cell Biol (2002) 156 (6): 969–981.
Article history
Received:
January 04 2002
Revision Received:
January 29 2002
Accepted:
January 29 2002
Citation
Valentina Sirri, Danièle Hernandez-Verdun, Pascal Roussel; Cyclin-dependent kinases govern formation and maintenance of the nucleolus . J Cell Biol 18 March 2002; 156 (6): 969–981. doi: https://doi.org/10.1083/jcb.200201024
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