title: Cyclin-dependent kinases govern formation and maintenance of the nucleolus.
abstract: 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.
authors.affiliation: Institut Jacques Monod, UMR 7592, 75251 Paris, France.
authors.forename: Valentina
authors.initials: V
authors.lastname: Sirri
authors.forename: Danièle
authors.initials: D
authors.lastname: Hernandez-Verdun
authors.forename: Pascal
authors.initials: P
authors.lastname: Roussel
mesh_terms: D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002451:Cell Compartmentation / Q000187:drug effects / Q000235:genetics*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics*; D002466:Cell Nucleolus / Q000201:enzymology* / Q000235:genetics / Q000648:ultrastructure; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D019926:Cyclin B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004275:DNA, Ribosomal / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000187:drug effects / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012335:RNA, Ribosomal / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D019926:Cyclin B; D004275:DNA, Ribosomal; D009687:Nuclear Proteins; D012335:RNA, Ribosomal; C107468:RRP1 protein, human; C047458:fibrillarin; D016203:CDC2 Protein Kinase; D018844:Cyclin-Dependent Kinases