Ribosome biogenesis lies at the nexus of various signaling pathways coordinating protein synthesis with cell growth and proliferation. This process is regulated by well-described transcriptional mechanisms, but a growing body of evidence indicates that other levels of regulation exist. Here we show that the Ras/mitogen-activated protein kinase (MAPK) pathway stimulates post-transcriptional stages of human ribosome synthesis. We identify RIOK2, a pre-40S particle assembly factor, as a new target of the MAPK-activated kinase RSK. RIOK2 phosphorylation by RSK promotes cytoplasmic maturation of late pre-40S particles, which is required for optimal protein synthesis and cell proliferation. RIOK2 phosphorylation facilitates its release from pre-40S particles and its nuclear re-import, prior to completion of small ribosomal subunits. Our results bring a detailed mechanistic link between the Ras/MAPK pathway and the maturation of human pre-40S particles, which open a hitherto poorly explored area of ribosome biogenesis.

中文翻译：

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RSK的RIOK2磷酸化促进人类小核糖体亚基的合成

核糖体的生物发生位于协调蛋白质合成与细胞生长和增殖的各种信号通路之间。该过程受众所周知的转录机制调控，但是越来越多的证据表明存在其他水平的调控。在这里，我们显示Ras /促分裂原激活的蛋白激酶（MAPK）途径刺激人类核糖体合成的转录后阶段。我们确定RIOK2，一个40S之前的颗粒装配因子，作为MAPK激活的激酶RSK的新目标。RSK引起的RIOK2磷酸化促进晚期40S之前的颗粒的胞质成熟，这是最佳蛋白质合成和细胞增殖所必需的。在完成小的核糖体亚基之前，RIOK2的磷酸化有助于其从40S之前的颗粒中释放并重新导入核中。