Promoter-proximal elongation regulates transcription in archaea

Fabian Blombach (), Thomas Fouqueau, Dorota Matelska, Katherine Smollett and Finn Werner ()
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Fabian Blombach: Division of Biosciences, Institute of Structural and Molecular Biology, University College London
Thomas Fouqueau: Division of Biosciences, Institute of Structural and Molecular Biology, University College London
Dorota Matelska: Division of Biosciences, Institute of Structural and Molecular Biology, University College London
Katherine Smollett: Division of Biosciences, Institute of Structural and Molecular Biology, University College London
Finn Werner: Division of Biosciences, Institute of Structural and Molecular Biology, University College London

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract Recruitment of RNA polymerase and initiation factors to the promoter is the only known target for transcription activation and repression in archaea. Whether any of the subsequent steps towards productive transcription elongation are involved in regulation is not known. We characterised how the basal transcription machinery is distributed along genes in the archaeon Saccharolobus solfataricus. We discovered a distinct early elongation phase where RNA polymerases sequentially recruit the elongation factors Spt4/5 and Elf1 to form the transcription elongation complex (TEC) before the TEC escapes into productive transcription. TEC escape is rate-limiting for transcription output during exponential growth. Oxidative stress causes changes in TEC escape that correlate with changes in the transcriptome. Our results thus establish that TEC escape contributes to the basal promoter strength and facilitates transcription regulation. Impaired TEC escape coincides with the accumulation of initiation factors at the promoter and recruitment of termination factor aCPSF1 to the early TEC. This suggests two possible mechanisms for how TEC escape limits transcription, physically blocking upstream RNA polymerases during transcription initiation and premature termination of early TECs.

Date: 2021
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DOI: 10.1038/s41467-021-25669-2

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