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 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. [Display omitted] •Decreased ribosome levels result in dose-dependent changes in gene expression•Ribosomal protein deficiency leads to strong secondary changes to the transcriptome•Mutation of genes for 60S proteins causes upregulation of protein-degradation genes•RPs are post-translationally regulated, with distinct outcomes from Rpl or Rps loss In this issue of Molecular Cell, Cheng et al. report specific and dose-dependent gene expression changes resulting from decreased ribosome levels, including distinct gene expression signatures resulting from loss of genes encoding members of either the large or small ribosomal subunit.