GSE121189
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. Overall design: 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