Endoribonuclease-mediated control of hns mRNA stability constitutes a key regulatory pathway for Salmonella Typhimurium pathogenicity island 1 expression

PLoS Pathog. 2021 Feb 1;17(2):e1009263. doi: 10.1371/journal.ppat.1009263. eCollection 2021 Feb.

Abstract

Bacteria utilize endoribonuclease-mediated RNA processing and decay to rapidly adapt to environmental changes. Here, we report that the modulation of hns mRNA stability by the endoribonuclease RNase G plays a key role in Salmonella Typhimurium pathogenicity. We found that RNase G determines the half-life of hns mRNA by cleaving its 5' untranslated region and that altering its cleavage sites by genome editing stabilizes hns mRNA, thus decreasing S. Typhimurium virulence in mice. Under anaerobic conditions, the FNR-mediated transcriptional repression of rnc encoding RNase III, which degrades rng mRNA, and simultaneous induction of rng transcription resulted in rapid hns mRNA degradation, leading to the derepression of genes involved in the Salmonella pathogenicity island 1 (SPI-1) type III secretion system (T3SS). Together, our findings show that RNase III and RNase G levels-mediated control of hns mRNA abundance acts as a regulatory pathway upstream of a complex feed-forward loop for SPI-1 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Binding Sites
  • DNA-Binding Proteins / genetics
  • Female
  • Gene Expression Regulation, Bacterial*
  • Genomic Islands*
  • Mice
  • Mice, Inbred BALB C
  • Oxygen / metabolism
  • RNA Stability*
  • RNA, Bacterial / metabolism*
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / pathogenicity*
  • Transcriptome
  • Type III Secretion Systems / genetics
  • Type III Secretion Systems / metabolism
  • Virulence / genetics

Substances

  • Bacterial Proteins
  • DNA-Binding Proteins
  • H-NS protein, bacteria
  • RNA, Bacterial
  • Type III Secretion Systems
  • Oxygen

Grants and funding

This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (grant no. 2018R1A5A1025077 and 2019R1A2C2084563 to K. L., grant no. NRF-2019R1F1A1062989 to Y. -H. K., and grant no. NRF-2019R1I1A1A01063517 to M. L.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.