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  • Review Article
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Diverse and unified mechanisms of transcription initiation in bacteria

Abstract

Transcription of DNA is a fundamental process in all cellular organisms. The enzyme responsible for transcription, RNA polymerase, is conserved in general architecture and catalytic function across the three domains of life. Diverse mechanisms are used among and within the different branches to regulate transcription initiation. Mechanistic studies of transcription initiation in bacteria are especially amenable because the promoter recognition and melting steps are much less complicated than in eukaryotes or archaea. Also, bacteria have critical roles in human health as pathogens and commensals, and the bacterial RNA polymerase is a proven target for antibiotics. Recent biophysical studies of RNA polymerases and their inhibition, as well as transcription initiation and transcription factors, have detailed the mechanisms of transcription initiation in phylogenetically diverse bacteria, inspiring this Review to examine unifying and diverse themes in this process.

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Fig. 1: Overview of the steps of bacterial transcription initiation and RNA polymerase.
Fig. 2: Towards structural elucidations of RNA polymerase initiation complexes.
Fig. 3: 50 years of studying σ.
Fig. 4: Structure-based model of open promoter complex formation highlighting RNA polymerase motions that lead to promoter melting.
Fig. 5: Factors that regulate the pool of holoenzymes.
Fig. 6: Diversity in bacterial RNAPs and their regulation.
Fig. 7: Inhibitors of RNA polymerase.

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Acknowledgements

The authors thank R. Landick, S. Darst and R. Froom for helpful discussions and copyediting. They apologize to colleagues whose work could not be cited owing to the scope and space limits of the Review. The authors are grateful for support from NIH grant 2-R01 GM114450 (E.A.C.) and the Charles H. Revson Foundation award CEN5650030 (H.B.).

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J.C., H.B. and E.A.C. researched data for article, discussed the content and wrote the article.

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Correspondence to Elizabeth A. Campbell.

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Glossary

Initiation factors

Factors that coordinate with RNA polymerase to facilitate the start of the transcription cycle.

Promoter melting

Process in which duplex promoter DNA is unwound during transcription initiation.

Abortive transcription

Process where RNA polymerase cycles between the initial transcribing complex and the open complex, leading to the release of short RNAs.

Scrunching

Process during transcription initiation in which the RNA polymerase pulls the downstream DNA into the active site, causing an expansion of the transcription bubble inside the RNA polymerase cleft.

Sugar puckers

Ring conformation of the deoxyribose or ribose sugar in DNA or RNA, respectively.

Stringent response

Bacterial response to stresses in the environment such as amino acid starvation.

σA

The housekeeping σ-factor in bacteria that controls the expression of most genes during growth.

Trigger loop

Mobile structural element in the RNA polymerase active centre that plays key roles in the nucleotide addition cycle.

Pyrophosphorolysis

The reverse polymerization reaction in which a pyrophosphate can cleave a phosphodiester bond at the 3′ end of an RNA.

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Chen, J., Boyaci, H. & Campbell, E.A. Diverse and unified mechanisms of transcription initiation in bacteria. Nat Rev Microbiol 19, 95–109 (2021). https://doi.org/10.1038/s41579-020-00450-2

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