Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Biology, Institute of Biochemistry, ETH, 8093 Zurich, Switzerland.
Mol Cell. 2019 Jan 3;73(1):36-47.e10. doi: 10.1016/j.molcel.2018.10.032. Epub 2018 Nov 29.
Levels of the ribosome, the conserved molecular machine that mediates translation, are tightly linked to cellular growth rate. In humans, ribosomopathies are diseases associated with cell-type-specific pathologies and reduced ribosomal protein (RP) levels. Because gene expression defects resulting from ribosome deficiency have not yet been experimentally defined, we systematically probed mRNA, translation, and protein signatures that were either unlinked from or linked to cellular growth rate in RP-deficient yeast cells. Ribosome deficiency was associated with altered translation of gene subclasses, and profound general secondary effects of RP loss on the spectrum of cellular mRNAs were seen. Among these effects, growth-defective 60S mutants increased synthesis of proteins involved in proteasome-mediated degradation, whereas 40S mutants accumulated mature 60S subunits and increased translation of ribosome biogenesis genes. These distinct signatures of protein synthesis suggest intriguing and currently mysterious differences in the cellular consequences of deficiency for small and large ribosomal subunits.
核糖体是一种介导翻译的保守分子机器，其水平与细胞生长速率密切相关。在人类中，核糖体病是与细胞类型特异性病理和核糖体蛋白 (RP) 水平降低相关的疾病。由于由于核糖体缺乏导致的基因表达缺陷尚未通过实验来定义，因此我们系统地探测了与细胞生长速率无关或相关的 mRNA、翻译和蛋白质特征在 RP 缺陷酵母细胞中。核糖体缺乏与基因亚类翻译的改变有关，并且在 RP 缺失对细胞 mRNA 谱的广泛的二次影响也很明显。其中，生长缺陷的 60S 突变体增加了参与蛋白酶体介导的降解的蛋白质的合成，而 40S 突变体则积累成熟的 60S 亚基并增加核糖体生物发生基因的翻译。这些不同的蛋白质合成特征表明，小核糖体亚基和大核糖体亚基的缺乏对细胞的影响存在有趣且目前神秘的差异。
