Depletion of ribosomal protein S19 causes a reduction of rRNA synthesis
Depletion of ribosomal protein S19 causes a reduction of rRNA synthesis
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DOI：
10.1038/srep35026
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发表时间：
2016-10-13
影响因子：
4.6
通讯作者：
Loreni, Fabrizio
中科院分区：
文献类型：
--
作者：
Juli, Giada;Gismondi, Angelo;Loreni, Fabrizio
核糖体生物合成通过提供增加的蛋白质合成能力在细胞生长中起关键作用。它需要核糖体蛋白（RP）和核糖体RNA（rRNA）的协调生产，包括后者的加工。在这里，我们表明，RPS19的耗竭导致红系和非红系起源的细胞系中rRNA合成的减少。在RPS6或RPL 11耗尽时观察到类似的效果。RPS19的缺乏不会改变rRNA的稳定性，而是导致RNA聚合酶I（Pol I）活性的抑制。事实上，核连续试验和ChIP实验的结果表明，在RPS19耗尽的细胞中，Pol I与rRNA基因的结合减少。在核糖体应激期间，Pol I、CDK2、AKT和AMPK的三种已知调节剂的磷酸化发生改变，并且可能参与观察到的下调。最后，来自钻石黑扇贫血（DBA）患者的RNA显示，平均而言，47S前体水平较低。这表明rRNA合成的抑制可能是DBA基础上的分子改变之一。
Ribosome biogenesis plays key roles in cell growth by providing increased capacity for protein synthesis. It requires coordinated production of ribosomal proteins (RP) and ribosomal RNA (rRNA), including the processing of the latter. Here, we show that, the depletion of RPS19 causes a reduction of rRNA synthesis in cell lines of both erythroid and non-erythroid origin. A similar effect is observed upon depletion of RPS6 or RPL11. The deficiency of RPS19 does not alter the stability of rRNA, but instead leads to an inhibition of RNA Polymerase I (Pol I) activity. In fact, results of nuclear run-on assays and ChIP experiments show that association of Pol I with the rRNA gene is reduced in RPS19-depleted cells. The phosphorylation of three known regulators of Pol I, CDK2, AKT and AMPK, is altered during ribosomal stress and could be involved in the observed downregulation. Finally, RNA from patients with Diamond Blackfan Anemia (DBA), shows, on average, a lower level of 47S precursor. This indicates that inhibition of rRNA synthesis could be one of the molecular alterations at the basis of DBA.