Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.30.2 (
endonuclease
)
18,621
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Posttranscriptional regulation plays an essential role in the quick adaptation of pathogenic bacteria to host environments, and RNases play key roles in this process by modifying small RNAs and mRNAs. We find that the
Pseudomonas aeruginosa
endonuclease
YbeY is required for rRNA processing and the bacterial virulence in a murine acute pneumonia model. Transcriptomic analyses reveal that knocking out the
ybeY
gene results in downregulation of oxidative stress response genes, including the catalase genes
katA
and
katB
Consistently, the
ybeY
mutant is more susceptible to H
2
O
2
and neutrophil-mediated killing. Overexpression of
katA
restores the bacterial tolerance to H
2
O
2
and neutrophil killing as well as virulence. We further find that the downregulation of the oxidative stress response genes is due to defective expression of the stationary-phase sigma factor RpoS. We demonstrate an autoregulatory mechanism of RpoS and find that
ybeY
mutation increases the level of a small RNA, ReaL, which directly represses the translation of
rpoS
through the 5'
UTR
of its mRNA and subsequently reduces the expression of the oxidative stress response genes.
In vitro
assays demonstrate direct degradation of ReaL by YbeY. Deletion of
reaL
or overexpression of
rpoS
in the
ybeY
mutant restores the bacterial tolerance to oxidative stress and the virulence. We also demonstrate that YbeZ binds to YbeY and is involved in the 16S rRNA processing and regulation of
reaL
and
rpoS
as well as the bacterial virulence. Overall, our results reveal pleiotropic roles of YbeY and the YbeY-mediated regulation of
rpoS
through ReaL.
IMPORTANCE
The increasing bacterial antibiotic resistance imposes a severe threat to human health. For the development of effective treatment and prevention strategies, it is critical to understand the mechanisms employed by bacteria to grow in the human body. Posttranscriptional regulation plays an important role in bacterial adaptation to environmental changes. RNases and small RNAs are key players in this regulation. In this study, we demonstrate critical roles of the RNase YbeY in the virulence of the pathogenic bacterium
Pseudomonas aeruginosa
We further identify the small RNA ReaL as the direct target of YbeY and elucidate the YbeY-regulated pathway on the expression of bacterial virulence factors. Our results shed light on the complex regulatory network of
P. aeruginosa
and indicate that inference with the YbeY-mediated regulatory pathway might be a valid strategy for the development of a novel treatment strategy.
...
PMID:Endoribonuclease YbeY Is Essential for RNA Processing and Virulence in Pseudomonas aeruginosa. 3260 82
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