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首页> 外文期刊>Molecular and Cellular Biology >Ribosome Synthesis-Unrelated Functions of the Preribosomal Factor Rrp12 in Cell Cycle Progression and the DNA Damage Response
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Ribosome Synthesis-Unrelated Functions of the Preribosomal Factor Rrp12 in Cell Cycle Progression and the DNA Damage Response

机译：核糖体合成前核糖体因子Rrp12在细胞周期进程和DNA损伤反应中的无关功能。

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摘要

Given the high metabolic cost required to generate ribosomes, it has been assumed that proteins involved in ribosome synthesis might establish functional cross talk with other intracellular processes to efficiently couple ribosome production and cell growth. However, such interconnections have remained elusive due to the difficulty in separating the intra- and extraribosomal roles of ribosome biogenesis factors. Using a yeast functional screen, I have discovered that Rrp12, a conserved protein involved in ribosome maturation and export, plays roles in the cell cycle and the DNA damage response. These results indicate that Rrp12 participates in a karyopherin Kap121-dependent import route that is crucial for nuclear sequestration of ribonucleotide reductase subunits and, thereby, ensures the proper kinetics of deoxyribonucleotide production during the cell cycle. Within this route, Rrp12 acts as a cofactor important for the full functionality of Kap121. This activity is mechanistically different from the known roles of Rrp12 in ribosome biogenesis. I propose that the functional duality of Rrp12 may couple the control of ribosome production to the regulation of other cellular processes during cell cycle progression.
机译：考虑到产生核糖体所需的高代谢成本，已经假定参与核糖体合成的蛋白质可能与其他细胞内过程建立功能性串扰，以有效地结合核糖体的产生和细胞生长。但是，由于难以分离核糖体生物发生因子的核糖体内和核糖体外作用，因此这种互连仍然难以捉摸。通过酵母功能筛选，我发现Rrp12是一种参与核糖体成熟和输出的保守蛋白，在细胞周期和DNA损伤反应中发挥作用。这些结果表明，Rrp12参与了核蛋白Kap121依赖性的导入途径，这对核糖核苷酸还原酶亚基的核螯合至关重要，从而确保了细胞周期中脱氧核糖核苷酸生产的适当动力学。在此路由范围内，Rrp12充当了辅助因子，对于Kap121的全部功能至关重要。这种活性在机制上不同于Rrp12在核糖体生物发生中的已知作用。我提出，Rrp12的功能对偶性可以将核糖体生产的控制与细胞周期进程中其他细胞过程的调节结合在一起。

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