Inhibiting ribosome assembly and ribosome translation have distinctly different effects on the abundance and paralogue composition of ribosomal protein mRNAs inSaccharomyces cerevisiae

Abstract

Many mutations in genes for ribosomal proteins and assembly factors cause cell stress and altered cell fate resulting in congenital diseases, collectively called ribosomopathies. Even though all such mutations depress the cell's protein synthesis capacity, they generate many different phenotypes, suggesting that the diseases are not due simply to insufficient protein synthesis capacity. To learn more, we have investigated how the global transcriptome in Saccharomyces cerevisiae responds to reduced protein synthesis generated in two different ways: abolishing the assembly of new ribosomes or inhibiting ribosomal function. Our results show that the mechanism by which protein synthesis is obstructed affects the ribosomal protein transcriptome differentially: ribosomal protein mRNA abundance increases during the abolition of ribosome formation but decreases during the inhibition of ribosome function. Interestingly, the ratio between mRNAs from some, but not all, paralogous genes encoding slightly different versions of a given r-protein change differently during the two types of stress, suggesting that specific ribosomal protein paralogues may contribute to the stress response. Unexpectedly, the abundance of transcripts for ribosome assembly factors and translation factors remains relatively unaffected by the stresses. On the other hand, the state of the translation apparatus does affect cell physiology: mRNA levels for some other proteins not directly related to the translation apparatus also change differentially, though not coordinately with the r-protein genes, in response to the stresses.