Regulation of multiple paralogs of a small subunit ribosomal protein in Francisella tularensis

Sierra S Schmidt1, Alexandra R Farah2,3, Aisling Macaraeg1

  • 1Department of Cell and Molecular Biology, University of Rhode Island, Kingston, RI 02881, USA.

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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