Specialized ribosomes: Ribosome heterogeneity and the translational control of mitochondrial and peroxisomal proteins

Genome duplication in eukaryotes created paralog pairs and isoforms of ribosomal proteins (RPs) that show high sequence similarity/identity. In yeast alone, 58 out of 79 RPs exist in paralog pairs thus allowing for the potential formation of ribosomes that differ vastly in protein composition, which may alter the recognition and translation of subsets of mRNAs. Previous works have shown that the deletion of individual paralogs can have different effects upon cellular processes, such as actin organization, bud site selection, and mRNA localization, although the mechanism remains unknown. Thus, whether specialized ribosomes (of defined composition) control mRNA translation was unclear until recently. By phenotyping yeast RP deletion libraries and using a non-biased method of translatome analysis, we have shown that the translation of numerous mitochondrial proteins is down-regulated in cells lacking specific RP paralogs, resulting in defects in respiration¹. Correspondingly, ribosomes containing these paralogs confer more efficient translation of mitochondrial proteins and show specific-sequence requirements for RNA selectivity. Additional studies demonstrate a requirement for specific RP paralogs in regulating the translation of peroxisomal proteins and peroxisome function, and a core set of paralogs appears to be required for regulating cellular responses to stress. Thus, paralog specificity controls the translation of subsets of mRNAs involved in maintaining homeostasis in response to environmental changes, as well, as changes in carbon source availability. Therefore, ribosome composition confers specialized functions and RP paralog specificity defines a novel means of translational control².

¹Segev and Gerst (2018) J. Cell Biol. 217:117-126

²Gerst (2018) Trends Genet. 34:832-845