Work

Activation of bacterial transcription by distortion of promoter base pairing

Year: 2025

Type: article

Abstract: Bacterial RNA polymerase binds and unwinds promoter DNA to initiate transcription. The process is often inefficient and can be stimulated by activator proteins. For example, many activators bind RNA polymerase and promoters simultaneously, stabilizing their interaction. Working with the multiple antibiotic resistance activator (MarA) protein of Escherichia coli, we have discovered an alternative mechanism. We show that, when bound upstream of the flgBCDEFGHIJ/KL operon, MarA perturbs base pairing adjacent to its DNA target. This compensates for inefficient duplex unwinding by RNA polymerase and, as a result, activates transcription. Consistent with our model, an appropriate base pair mismatch mimics the effect of, and removes the need for, MarA. As many regulators alter DNA conformation, we suggest that this mechanism of activation could be commonplace.

Source: Nucleic Acids Research

DOI: 10.1093/nar/gkaf1424

Authors: Ksenia M Klimova, David Forrest, Prateek Sharma, James R J Haycocks, David C Grainger

Institution: University of Birmingham

Language: English

Topic: Bacterial Genetics and Biotechnology

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,992

Funders: Wellcome Trust, University of Birmingham, Darwin Trust of Edinburgh