Repression of RNA polymerase by the archaeo-viral regulator ORF145/RIP

Carol Sheppard, Fabian Blombach, Adam Belsom, Sarah Schulz, Tina Daviter, Katherine Smollett, Emilie Mahieu, Susanne Erdmann, Philip Tinnefeld, Roger Garrett, Dina Grohmann, Juri Rappsilber and Finn Werner ()
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Carol Sheppard: Institute of Structural and Molecular Biology, University College London
Fabian Blombach: Institute of Structural and Molecular Biology, University College London
Adam Belsom: Wellcome Trust Centre for Cell Biology, University of Edinburgh
Sarah Schulz: Physikalische und Theoretische Chemie—NanoBioSciences, Technische Universität Braunschweig
Tina Daviter: Institute of Structural and Molecular Biology, University College London
Katherine Smollett: Institute of Structural and Molecular Biology, University College London
Emilie Mahieu: Institute of Structural and Molecular Biology, University College London
Susanne Erdmann: University of Copenhagen
Philip Tinnefeld: Physikalische und Theoretische Chemie—NanoBioSciences, Technische Universität Braunschweig
Roger Garrett: University of Copenhagen
Dina Grohmann: Physikalische und Theoretische Chemie—NanoBioSciences, Technische Universität Braunschweig
Juri Rappsilber: Wellcome Trust Centre for Cell Biology, University of Edinburgh
Finn Werner: Institute of Structural and Molecular Biology, University College London

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract Little is known about how archaeal viruses perturb the transcription machinery of their hosts. Here we provide the first example of an archaeo-viral transcription factor that directly targets the host RNA polymerase (RNAP) and efficiently represses its activity. ORF145 from the temperate Acidianus two-tailed virus (ATV) forms a high-affinity complex with RNAP by binding inside the DNA-binding channel where it locks the flexible RNAP clamp in one position. This counteracts the formation of transcription pre-initiation complexes in vitro and represses abortive and productive transcription initiation, as well as elongation. Both host and viral promoters are subjected to ORF145 repression. Thus, ORF145 has the properties of a global transcription repressor and its overexpression is toxic for Sulfolobus. On the basis of its properties, we have re-named ORF145 RNAP Inhibitory Protein (RIP).

Date: 2016
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DOI: 10.1038/ncomms13595

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