Sirri Valentina, Hernandez-Verdun Danièle, Roussel Pascal
Institut Jacques Monod, UMR 7592, 75251 Paris, France.
J Cell Biol. 2002 Mar 18;156(6):969-81. doi: 10.1083/jcb.200201024.
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.
在高等真核细胞中，核仁是一个在间期开始时组装、在间期维持、在有丝分裂期间解体的核区室。即使其结构组织似乎与其在核糖体生物合成中的功能不可分离，但调控核仁形成和维持的机制仍未阐明。为了确定细胞周期调节因子是否参与其中，我们研究了细胞周期蛋白依赖性激酶（CDK）在核糖体生物合成和核仁组织中的假定作用。在有丝分裂期间抑制CDK1-细胞周期蛋白B会导致rDNA转录恢复，但不足以诱导前体rRNA的正确加工以及加工机器完全重新定位到rDNA转录位点。同样，在有丝分裂退出时，晚期加工机器的易位和前体rRNA加工都会被CDK抑制剂以可逆的方式损害。因此，CDK活性似乎对于功能性核仁的构建不可或缺。此外，在间期细胞中抑制CDK也会阻碍前体rRNA的正确加工，并导致核仁显著解体。因此，我们提出调控功能性核仁形成和维持的机制涉及CDK活性，并将细胞周期与核糖体生物合成联系起来。
