Endogenous rRNA sequence variation can regulate stress response gene expression and phenotype

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.学界主流观点认为，核糖体的组成与功能均保持一致。本研究显示，大肠杆菌（E. coli）中营养限制诱导的应激会改变核糖体DNA操纵子的相对表达水平，进而改变活跃翻译的核糖体池中核糖体RNA（rRNA）的组成。上调最显著的操纵子编码独特的16S rRNA基因rrsH，该基因以小核糖体亚基内的保守序列变异为特征。携带rrsH的核糖体会影响功能协同的基因集的转录与翻译，并改变RpoSσ因子的水平——后者是全局应激反应的主调控因子。这些效应与抗生素敏感性、生物膜形成以及细胞运动性的表型变化相关，且受应激反应蛋白RelA、RelE，以及代谢酶与毒力相关蛋白AdhE的调控。本研究证实，核糖体中内源性编码的天然存在的rRNA序列变异，能够调控核糖体功能、基因表达调控的核心环节以及细胞生理活动。