Small and large ribosomal subunit deficiencies lead to distinct gene expression signatures that reflect cellular growth rate

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 or linked to cellular growth rate in RP-deficient yeast cells. Ribosome concentration was seen to be associated with translation of gene sub-classes, 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（ribosome）作为介导翻译过程的保守分子机器，其丰度与细胞生长速率紧密相关。在人类中，核糖体病（ribosomopathy）是一类与细胞类型特异性病理及核糖体蛋白（RP）水平降低相关的疾病。鉴于核糖体缺陷引发的基因表达缺陷尚未经实验明确，本研究在核糖体蛋白缺陷的酵母细胞中，系统性探查了与细胞生长速率相关或不相关的mRNA、翻译及蛋白质特征谱。研究发现，核糖体浓度与基因子类的翻译水平相关，且核糖体蛋白缺失会对细胞mRNA谱产生显著的全局性次级效应。在这些效应中，生长缺陷型60S亚基突变体可提升参与蛋白酶体介导降解过程的蛋白质合成量，而40S亚基突变体则会积累成熟60S亚基，并增强核糖体生物发生基因的翻译效率。上述蛋白质合成的独特特征谱表明，核糖体小亚基与大亚基缺陷所引发的细胞效应存在引人关注且目前尚未阐明的差异。