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. Sequencing of mRNA molecules and ribosome footprints in strains deleted for different ribosomal protein-encoding genes to identify changes in gene expression that are linked to total translation level

核糖体（ribosome）作为介导翻译过程的保守分子机器，其丰度水平与细胞生长速率密切相关。在人类中，核糖体病（ribosomopathy）是一类伴随细胞类型特异性病理表型、且核糖体蛋白（RP）水平降低的疾病。由于核糖体缺陷引发的基因表达缺陷尚未经实验阐明，本研究系统探究了核糖体蛋白缺陷型酵母细胞中，与细胞生长速率相关及无关的信使RNA（mRNA）、翻译过程及蛋白质特征谱。研究发现，核糖体浓度与特定基因子类的翻译过程相关，且核糖体蛋白缺失会对细胞mRNA整体谱产生显著且广泛的次级效应。其中，生长缺陷型60S核糖体亚基突变体可上调蛋白酶体介导的降解通路相关蛋白的合成，而40S核糖体亚基突变体则会积累成熟的60S亚基，并增强核糖体生物发生基因的翻译效率。这些迥异的蛋白质合成特征谱，提示核糖体小亚基与大亚基缺陷所引发的细胞效应存在目前尚不明晰的有趣差异。本研究对不同核糖体蛋白编码基因缺失菌株的mRNA分子及核糖体足迹（ribosome footprint）进行测序，以鉴定与总翻译水平相关的基因表达变化。