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Mediator structure and rearrangements required for holoenzyme formation

Author

Listed:
  • 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
    University of Kansas Medical Center)

  • Kenji Murakami

    (Stanford University School of Medicine
    †Present addresses: Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA (K.M.); Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado 80045, USA (F.J.A.).)

  • Ronald C. Conaway

    (Stowers Institute for Medical Research
    University of Kansas Medical Center)

  • Joan W. Conaway

    (Stowers Institute for Medical Research
    University of Kansas Medical Center)

  • Francisco J. Asturias

    (The Scripps Research Institute
    †Present addresses: Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA (K.M.); Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado 80045, USA (F.J.A.).)

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.

Suggested Citation

  • 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 & Francisco J. Asturias, 2017. "Mediator structure and rearrangements required for holoenzyme formation," Nature, Nature, vol. 544(7649), pages 196-201, April.
    • Handle: RePEc:nat:nature:v:544:y:2017:i:7649:d:10.1038_nature21393
    DOI: 10.1038/nature21393
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    Cited by:

    1. Alex Z. Kadhim & Ben Vanderkruk & Samantha Mar & Meixia Dan & Katarina Zosel & Eric E. Xu & Rachel J. Spencer & Shugo Sasaki & Xuanjin Cheng & Shannon L. J. Sproul & Thilo Speckmann & Cuilan Nian & Ro, 2024. "Transcriptional coactivator MED15 is required for beta cell maturation," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Kadir Buyukcelebi & Xintong Chen & Fatih Abdula & Hoda Elkafas & Alexander James Duval & Harun Ozturk & Fidan Seker-Polat & Qiushi Jin & Ping Yin & Yue Feng & Serdar E. Bulun & Jian Jun Wei & Feng Yue, 2023. "Engineered MED12 mutations drive leiomyoma-like transcriptional and metabolic programs by altering the 3D genome compartmentalization," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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