Differential expression of duplicated ribosomal protein genes modifies ribosome composition in response to stress.

In Saccharomyces cerevisiae, most ribosomal proteins are synthesized from duplicated genes, increasing the potential for ribosome heterogeneity. However, the contribution of these duplicated genes to ribosome production and the mechanism determining their relative expression remain unclear. Here we demonstrate that in most cases, one of the two gene copies generate the bulk of the active ribosomes under normal growth conditions, while the other copy is favored only under stress. To understand the origin of these differences in paralog expression and their contribution to ribosome heterogeneity we used RNA polymerase II ChIP-Seq, RNA-seq, polyribosome association and peptide-based mass-spectrometry to compare their transcription potential, splicing, mRNA abundance, translation potential, protein abundance and incorporation into ribosomes. In normal conditions a post-transcriptional expression hierarchy of the duplicated ribosomal protein genes is the product of the efficient splicing, high stability and efficient translation of the major paralog mRNA. Exposure of the cell to stress modifies the expression ratio of the paralogs by repressing the expression of the major paralog and thus increasing the number of ribosomes carrying the minor paralog. Together the data indicate that duplicated ribosomal protein genes underlie a modular network permitting the modification of ribosome composition in response to changing growth conditions.