General Transcription Factor fromE. coliwith a Distinct Mechanism of Action

Abstract

AbstractGene expression inE. coliis 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) σ70holoenzyme. Structural and biochemical analysis of CedA bound to RNAP reveal that it bridges distant domains of β and σ70subunits to stabilize an open-promoter complex. Remarkably, CedA does so without contacting DNA. We further show thatcedAis 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.One sentence summaryAn integrated structure-function approach uncovers CedA as a general transcription initiation factor inE. coliand elucidates its multifaceted role and unique mechanism.