Stress-induced ribosomal heterogeneity in Saccharomyces cerevisiae: from protein paralogs to regulatory noncoding RNAs.

Ribosomes, once considered uniform protein biosynthesis machines, are now recognized as heterogeneous and dynamic entities with specialized functions. In Saccharomyces cerevisiae, ribosomal heterogeneity arises from variability in ribosomal protein (RP) composition, rRNA sequence polymorphisms, post-transcriptional modifications, and associations with ribosome-associated factors and noncoding RNAs. RP gene (RPG) paralogs and their differential expression influence growth, stress resistance, and drug responses. Introns and untranslated regions in RPGs regulate expression under stress, while ribosome composition adjusts to environmental cues via altered RP stoichiometry and post-translational modifications, such as phosphorylation and ubiquitination. Additionally, ribosome-associated factors contribute to selective translation of specific mRNA subsets. Ribosomal RNA heterogeneity, though less studied in yeast, is evident through polymorphisms in rDNA arrays and post-transcriptional modifications like pseudouridylation and 2'-O-ribose methylation. Furthermore, transient associations with small noncoding RNAs (e.g. tRNA-, snoRNA-, and mRNA-derived fragments) modulate translation in a stress-dependent manner, supporting the concept of specialized ribosomes. Despite growing evidence, functional significance of ribosome specialization remains under debate. Future research aims to uncover the extent, regulation, and biological roles of ribosome heterogeneity across organisms and conditions. Emerging tools such as ribosome sequencing, single-molecule fluorescence resonance energy transfer, and single-molecule fluorescence resonance energy transfer offer promising avenues to resolve these questions and reveal how specialized ribosomes contribute to adaptive gene expression.