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bioRxiv · 10.1101/859132

Structural basis of RNA Polymerase III transcription repression by Maf1

Vorländer, M. K.·Baudin, F.·Moir, R. D.·Wetzel, R.·Hagen, W. J. H.·Willis, I. M.·Müller, C. W.
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Abstract

Maf1 is a highly conserved central regulator of transcription by RNA polymerase III (Pol III), and Maf1 activity influences a wide range of phenotypes from metabolic efficiency to lifespan. Here, we present a 3.3 [A] cryo-EM structure of yeast Maf1 bound to Pol III, which establishes how Maf1 achieves transcription repression. In the Maf1-bound state, Pol III elements that are involved in transcription initiation are sequestered, and the active site is sealed off due to ordering of the mobile C34 winged helix 2 domain. Specifically, the Maf1 binding site overlaps with the binding site of the Pol III transcription factor TFIIIB and DNA in the pre-initiation complex, rationalizing that binding of Maf1 and TFIIIB to Pol III are mutually exclusive. We validate our structure using variants of Maf1 with impaired transcription-inhibition activity. These results reveal the exact mechanism of Pol III inhibition by Maf1, and rationalize previous biochemical data.

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Vorländer, M. K., Baudin, F., Moir, R. D., Wetzel, R., Hagen, W. J. H., Willis, I. M., Müller, C. W.. 2019-11-29. Structural basis of RNA Polymerase III transcription repression by Maf1. https://doi.org/10.1101/859132

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