Regulation of multiple paralogs of a small subunit ribosomal protein in Francisella tularensis
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Updated: Sep 15, 2025

Method for the Isolation of Francisella tularensis Outer Membranes
Published on: June 29, 2010
Sierra S Schmidt1, Alexandra R Farah2,3, Aisling Macaraeg1
1Department of Cell and Molecular Biology, University of Rhode Island, Kingston, RI 02881, USA.
Abstract:
Francisella tularensis is a highly infectious human pathogen that must replicate inside macrophage to cause disease. The ribosomes of F. tularensis can incorporate one of three different paralogs for the small ribosomal subunit protein bS21. One of these paralogs positively impacts translation of key virulence genes and promotes intramacrophage replication. Although ribosomal bS21 content influences F. tularensis virulence, the factors that control bS21 paralog production are not well understood. Here, we reveal that all three bS21 proteins influence the transcript abundance of the paralog important for virulence, bS21-2. In contrast, the other bS21 paralogs (bS21-1 and bS21-3) do not affect their own production. We further determined that the leader sequence of the bS21-2 mRNA is sufficient for bS21-mediated repression of mRNA abundance, suggesting that bS21-2 is autogenously regulated. Yet we determined that the increase in bS21-2-encoding mRNA is not reflected by increased protein production, suggesting that translation of this transcript is controlled by other factors. Finally, we found that bS21-2 exerts at least some of its effects on the bS21-2 transcript by decreasing its stability. Together, our findings suggest that F. tularensis integrates multiple signals into a regulatory network to control the appropriate production of each bS21 paralog, and particularly the paralog important for virulence, bS21-2. This regulatory network in turn may control ribosomal heterogeneity and virulence gene expression.
Insights
Francisella tularensis uses multiple bS21 proteins to control virulence. The bS21-2 paralog is key for intramacrophage replication and its production is tightly regulated through mRNA stability and autogenous control.
Area of Science:
- Microbiology
- Molecular Biology
- Bacterial Pathogenesis
Background:
- Francisella tularensis is an infectious pathogen requiring macrophage replication for disease.
- Ribosomes incorporate one of three bS21 paralogs, impacting virulence gene translation and replication.
- bS21 paralog production control in F. tularensis is not fully understood.
Purpose of the Study:
- Investigate the regulatory mechanisms controlling bS21 paralog production in F. tularensis.
- Determine how bS21 paralogs influence each other's transcript abundance.
- Elucidate the role of the bS21-2 paralog in regulating its own production and virulence.
Main Methods:
- Analysis of bS21 paralog transcript abundance under different conditions.
- mRNA leader sequence analysis for autogenous regulation.
- Assessment of mRNA stability and translation efficiency.
Main Results:
- All three bS21 proteins affect bS21-2 transcript levels, while other paralogs do not regulate their own production.
- The bS21-2 mRNA leader sequence mediates autogenous repression of transcript abundance.
- Increased bS21-2 mRNA does not correlate with increased protein, indicating translational control.
- bS21-2 decreases bS21-2 transcript stability, contributing to its regulatory effects.
Conclusions:
- F. tularensis employs a regulatory network to control bS21 paralog production, particularly the virulence-associated bS21-2.
- This network integrates signals to manage ribosomal heterogeneity and virulence gene expression.
- Understanding bS21 regulation offers insights into F. tularensis pathogenesis and potential therapeutic targets.
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