Physical and functional interaction between pes1 and bop1 in mammalian ribosome biogenesis

Physical and functional interaction between pes1 and bop1 in mammalian ribosome biogenesis
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DOI:
10.1016/j.molcel.2004.05.020
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发表时间:
2004-07-02
期刊:
影响因子:
16
通讯作者:
Pestov, DG
Pestov, DG
中科院分区:
生物学1区
文献类型:
--
作者:
Lapik, YR;Fernandes, CJ;Pestov, DG

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哺乳动物核糖体生物发生的分子机制在很大程度上仍未被探索。在这里,我们开发了一系列由转座子衍生的Pes1显性突变体,Pes1是斑马鱼Pescadillo和酵母Nop7p的小鼠同源物,与核糖体生物发生和细胞增殖控制有关。6个Pes1突变体因其可逆阻滞细胞周期的能力而被选择,也损害了小鼠细胞中28S和5.8S rnas的成熟。我们发现Pes1与核仁蛋白Bop1物理相互作用,两种蛋白指导共同的pre-rRNA加工步骤。与Bop1的相互作用是Pes1有效结合到核仁核糖体前复合物的必要条件。与Bop1相互作用缺陷的Pes1突变体失去了影响rRNA成熟和细胞周期的能力。这些数据表明,Pes1和Bop1的协同作用对于60S核糖体亚基的生物发生是必要的。
Molecular mechanisms of mammalian ribosome biogenesis remain largely unexplored. Here we develop a series of transposon-derived dominant mutants of Pes1, the mouse homolog of the zebrafish Pescadillo and yeast Nop7p implicated in ribosome biogenesis and cell proliferation control. Six Pes1 mutants selected by their ability to reversibly arrest the cell cycle also impair maturation of the 28S and 5.8S rRNAs in mouse cells. We show that Pes1 physically interacts with the nucleolar protein Bop1, and both proteins direct common pre-rRNA processing steps. Interaction with Bop1 is essential for the efficient incorporation of Pes1 into nucleolar preribosomal complexes. Pes1 mutants defective for the interaction with Bop1 lose the ability to affect rRNA maturation and the cell cycle. These data show that coordinated action of Pes1 and Bop1 is necessary for the biogenesis of 60S ribosomal subunits.