Mediator structure and rearrangements required for holoenzyme formation

Kuang-Lei Tsai, Xiaodi Yu, Sneha Gopalan, Ti-Chun Chao, Ying Zhang, Laurence Florens, Michael P. Washburn, Kenji Murakami, Ronald C. Conaway, Joan W. Conaway and Francisco J. Asturias ()
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Kuang-Lei Tsai: The Scripps Research Institute
Xiaodi Yu: The Scripps Research Institute
Sneha Gopalan: Stowers Institute for Medical Research
Ti-Chun Chao: University of California San Diego School of Medicine
Ying Zhang: Stowers Institute for Medical Research
Laurence Florens: Stowers Institute for Medical Research
Michael P. Washburn: Stowers Institute for Medical Research
Kenji Murakami: Stanford University School of Medicine
Ronald C. Conaway: Stowers Institute for Medical Research
Joan W. Conaway: Stowers Institute for Medical Research
Francisco J. Asturias: The Scripps Research Institute

Nature, 2017, vol. 544, issue 7649, 196-201

Abstract: Abstract The conserved Mediator co-activator complex has an essential role in the regulation of RNA polymerase II transcription in all eukaryotes. Understanding the structure and interactions of Mediator is crucial for determining how the complex influences transcription initiation and conveys regulatory information to the basal transcription machinery. Here we present a 4.4 Å resolution cryo-electron microscopy map of Schizosaccharomyces pombe Mediator in which conserved Mediator subunits are individually resolved. The essential Med14 subunit works as a central backbone that connects the Mediator head, middle and tail modules. Comparison with a 7.8 Å resolution cryo-electron microscopy map of a Mediator–RNA polymerase II holoenzyme reveals that changes in the structure of Med14 facilitate a large-scale Mediator rearrangement that is essential for holoenzyme formation. Our study suggests that access to different conformations and crosstalk between structural elements are essential for the Mediator regulation mechanism, and could explain the capacity of the complex to integrate multiple regulatory signals.

Date: 2017
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DOI: 10.1038/nature21393

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