Structures of the RNA polymerase-σ54 reveal new and conserved regulatory strategies

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Science  21 Aug 2015:
Vol. 349, Issue 6250, pp. 882-885
DOI: 10.1126/science.aab1478

Keeping gene transcription in check

Transcription of all genes is carried out by RNA polymerase (RNAP). The enzyme is thus a pivotal regulation point for many cell and developmental processes. In bacteria, sigma factors play a vital role in transcription regulation, with σ54 being critical for transcription of many stress response genes. Yang et al. determined the x-ray crystal structure of RNAP bound to σ54, as well as promoter DNA. In the initial inhibited state of the RNAP-σ54 complex, the σ54 blocks the template DNA from entering the RNAP active site and the downstream DNA channel.

Science, this issue p. 882


Transcription by RNA polymerase (RNAP) in bacteria requires specific promoter recognition by σ factors. The major variant σ factor (σ54) initially forms a transcriptionally silent complex requiring specialized adenosine triphosphate–dependent activators for initiation. Our crystal structure of the 450-kilodalton RNAP-σ54 holoenzyme at 3.8 angstroms reveals molecular details of σ54 and its interactions with RNAP. The structure explains how σ54 targets different regions in RNAP to exert its inhibitory function. Although σ54 and the major σ factor, σ70, have similar functional domains and contact similar regions of RNAP, unanticipated differences are observed in their domain arrangement and interactions with RNAP, explaining their distinct properties. Furthermore, we observe evolutionarily conserved regulatory hotspots in RNAPs that can be targeted by a diverse range of mechanisms to fine tune transcription.

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