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General transcription factor from Escherichia coli with a distinct mechanism of action
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Journal Article
General transcription factor from Escherichia coli with a distinct mechanism of action
2024
Overview
Gene expression in
Escherichia coli
is controlled by well-established mechanisms that activate or repress transcription. Here, we identify CedA as an unconventional transcription factor specifically associated with the RNA polymerase (RNAP) σ
70
holoenzyme. Structural and biochemical analysis of CedA bound to RNAP reveal that it bridges distant domains of β and σ
70
subunits to stabilize an open-promoter complex. CedA does so without contacting DNA. We further show that
cedA
is strongly induced in response to amino acid starvation, oxidative stress and aminoglycosides. CedA provides a basal level of tolerance to these clinically relevant antibiotics, as well as to rifampicin and peroxide. Finally, we show that CedA modulates transcription of hundreds of bacterial genes, which explains its pleotropic effect on cell physiology and pathogenesis.
Here, using proteomics, next-generation sequencing, biochemistry and cryo-EM, the authors delineate the role of CedA as an unconventional transcription factor in
Escherichia
coli,
which protects from different stressors, including antibiotics, by regulating the transcriptional landscape.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Bacterial Proteins - metabolism
/ Biomedical and Life Sciences
/ DNA-Directed RNA Polymerases - metabolism
/ E coli
/ Escherichia coli - metabolism
/ Escherichia coli Proteins - metabolism
/ Rifampin
/ Transcription Factors - genetics
/ Transcription Factors - metabolism
/ Transcription Factors, General - genetics
