RNA Thermometers in Bacterial Virulence Regulation

RNA thermometers are cis-acting RNA elements located in the 5′-untranslated region of bacterial mRNAs that undergo temperature-dependent structural rearrangements to control translation initiation. At environmental temperatures, these structures sequester the ribosome-binding site, repressing synthesis of factors required for host adaptation. Upon a shift to host body temperature, local unfolding exposes the Shine–Dalgarno sequence and enables rapid translation of virulence determinants. This post-transcriptional sensing mechanism complements protein-based regulation, ensuring precise timing of pathogenic programmes. A diverse array of thermometers has been described, including FourU motifs, hairpin elements and unique intergenic thermosensors, each tailored to specific virulence genes such as iron-acquisition receptors, oxidative stress enzymes and type III secretion regulators.

Functionally, RNA thermometers allow bacteria to interpret temperature as a proxy for host entry, synchronising expression of adhesins, toxins and immune-evasion systems. By minimising the metabolic cost of constitutive expression and enabling swift adaptation to thermal fluctuations, these elements confer a significant evolutionary advantage. Understanding RNA thermometer diversity and mechanism holds global significance, revealing novel targets for antimicrobial development and informing strategies to mitigate emerging pathogens under climate change.

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Technical terms

RNA thermometer: A cis-acting RNA element that alters secondary structure in response to temperature changes, modulating ribosome access and translation initiation.

5′-untranslated region (5′-UTR): The non-coding sequence at the start of an mRNA that can contain regulatory elements affecting translation.

Ribosome-binding site (Shine–Dalgarno sequence): A purine-rich motif in bacterial mRNA that guides ribosome positioning for translation initiation.

FourU element: An RNA thermometer motif comprising consecutive uracil residues that occlude the ribosome-binding site at low temperature.

Thermo-labile regulator: A protein whose stability or activity is sensitive to temperature, influencing transcriptional control in response to thermal cues.

References

1. Temperature sensing and virulence regulation in pathogenic bacteria. Trends in Microbiology (2024).
2. The oxidative stress response, in particular the katY gene, is temperature-regulated in Yersinia pseudotuberculosis. PLOS Genetics (2023).
3. Concerted Actions of a Thermo-labile Regulator and a Unique Intergenic RNA Thermosensor Control Yersinia Virulence. PLOS Pathogens (2012).
4. RNA-Mediated Thermoregulation of Iron-Acquisition Genes in Shigella dysenteriae and Pathogenic Escherichia coli. PLOS ONE (2013).