Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houston, Texas 77030, USA.
Mol Cell Biol. 2010 Sep;30(18):4404-14. doi: 10.1128/MCB.00358-10. Epub 2010 Jul 20.
Ribosome biogenesis is a highly regulated process ensuring that cell growth (increase in biomass) is coordinated with cell proliferation. The formation of eukaryotic ribosomes is a multistep process initiated by the transcription and processing of rRNA in the nucleolus. Concomitant with this, several preribosomal particles, which transiently associate with numerous nonribosomal factors before mature 60S and 40S subunits are formed and exported in the cytoplasm, are generated. Here we identify Las1L as a previously uncharacterized nucleolar protein required for ribosome biogenesis. Depletion of Las1L causes inhibition of cell proliferation characterized by a G1 arrest dependent on the tumor suppressor p53. Moreover, we demonstrate that Las1L is crucial for ribosome biogenesis and that depletion of Las1L leads to inhibition of rRNA processing and failure to synthesize the mature 28S rRNA. Taken together, our data demonstrate that Las1L is essential for cell proliferation and biogenesis of the 60S ribosomal subunit.
核糖体生物发生是一个高度调控的过程,确保细胞生长(生物量增加)与细胞增殖相协调。真核核糖体的形成是一个多步骤的过程,由核仁中 rRNA 的转录和加工启动。与此同时,在成熟的 60S 和 40S 亚基形成并在细胞质中输出之前,会产生几个暂时与许多非核糖体因子结合的前核糖体颗粒。在这里,我们鉴定出 Las1L 是一种以前未被表征的核仁蛋白,它是核糖体生物发生所必需的。Las1L 的耗竭会导致细胞增殖受到抑制,其特征是依赖肿瘤抑制因子 p53 的 G1 期停滞。此外,我们证明 Las1L 对核糖体生物发生至关重要,并且 Las1L 的耗竭会导致 rRNA 加工抑制和无法合成成熟的 28S rRNA。总之,我们的数据表明 Las1L 是细胞增殖和 60S 核糖体亚基生物发生所必需的。