Endoribonuclease-mediated control of hns mRNA stability constitutes a key regulatory pathway for Salmonella Typhimurium pathogenicity island 1 expressionopen access
- Authors
- Lee, Minho; Ryu, Minkyung; Joo, Minju; Seo, Young-Jin; Lee, Jaejin; Kim, Hong-Man; Shin, Eunkyoung; Yeom, Ji-Hyun; Kim, Yong-Hak; Bae, Jeehyeon; Lee Kangseok
- Issue Date
- Feb-2021
- Publisher
- Public Library of Science
- Citation
- PLoS Pathogens, v.17, no.2
- Journal Title
- PLoS Pathogens
- Volume
- 17
- Number
- 2
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/48066
- DOI
- 10.1371/journal.ppat.1009263
- ISSN
- 1553-7366
1553-7374
- Abstract
- Author summary Recent studies have shown that pathogenic bacteria with ribonuclease mutations display attenuated virulence, impaired mobility, and reduced proliferation in host cells. However, the molecular mechanisms underlying ribonuclease-associated pathogenesis have not yet been characterised. Here, we provide strong experimental evidence that the coordinated modulation of endoribonuclease activity constitutes an additional regulatory layer upstream of a complex feed-forward loop controlling global regulatory systems in the Salmonella pathogenicity island 1 (SPI-1) type III secretion system (T3SS). In addition, we showed that this regulatory pathway plays a key role in the virulence of S. Typhimurium in the host. Thus, our study improves the understanding of the mechanisms through which bacterial pathogens sense the host environment and respond precisely by expressing gene products required for adaptation to that particular niche. 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.
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Collections - College of Pharmacy > School of Pharmacy > 1. Journal Articles
- College of Natural Sciences > Department of Life Science > 1. Journal Articles
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