Endogenous rRNA sequence variation can regulate stress response gene expression and phenotype. Escherichia coli str. K-12 substr. MG1655

Prevailing dogma holds that ribosomes are uniform in composition and function. Here, we show that nutrient limitation-induced stress in E. coli changes the relative expression of ribosomal DNA operons to alter the ribosomal RNA (rRNA) composition within the actively translating ribosome pool. The most upregulated operon encodes the unique 16S rRNA gene, rrsH, distinguished by conserved sequence variation within the small ribosomal subunit. rrsH-bearing ribosomes affect the transcription and translation of functionally coherent gene sets and alter the levels of the RpoS sigma factor, the master regulator of the general stress response. These impacts are associated with phenotypic changes in antibiotic sensitivity, biofilm formation, and cell motility, and are regulated by stress response proteins, RelA and RelE, as well as the metabolic enzyme and virulence-associated protein, AdhE. These findings establish that endogenously encoded, naturally occurring rRNA sequence variation in the ribosome can modulate ribosome function, central aspects of gene expression regulation, and cellular physiology.