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Phosphorylation induces sequence-specific conformational switches in the RNA polymerase II C-terminal domain

Author

Listed:
  • Eric B. Gibbs

    (The Pennsylvania State University)

  • Feiyue Lu

    (Huck Institutes of the Life Sciences, The Pennsylvania State University
    Center for Eukaryotic Gene Regulation, The Pennsylvania State University)

  • Bede Portz

    (Center for Eukaryotic Gene Regulation, The Pennsylvania State University)

  • Michael J. Fisher

    (Center for Eukaryotic Gene Regulation, The Pennsylvania State University)

  • Brenda P. Medellin

    (University of Texas at Austin
    Institute for Cellular and Molecular Biology, University of Texas at Austin)

  • Tatiana N. Laremore

    (Huck Institutes of the Life Sciences, The Pennsylvania State University)

  • Yan Jessie Zhang

    (University of Texas at Austin
    Institute for Cellular and Molecular Biology, University of Texas at Austin)

  • David S. Gilmour

    (Center for Eukaryotic Gene Regulation, The Pennsylvania State University)

  • Scott A. Showalter

    (The Pennsylvania State University
    Center for Eukaryotic Gene Regulation, The Pennsylvania State University)

Abstract

The carboxy-terminal domain (CTD) of the RNA polymerase II (Pol II) large subunit cycles through phosphorylation states that correlate with progression through the transcription cycle and regulate nascent mRNA processing. Structural analyses of yeast and mammalian CTD are hampered by their repetitive sequences. Here we identify a region of the Drosophila melanogaster CTD that is essential for Pol II function in vivo and capitalize on natural sequence variations within it to facilitate structural analysis. Mass spectrometry and NMR spectroscopy reveal that hyper-Ser5 phosphorylation transforms the local structure of this region via proline isomerization. The sequence context of this switch tunes the activity of the phosphatase Ssu72, leading to the preferential de-phosphorylation of specific heptads. Together, context-dependent conformational switches and biased dephosphorylation suggest a mechanism for the selective recruitment of cis-proline-specific regulatory factors and region-specific modulation of the CTD code that may augment gene regulation in developmentally complex organisms.

Suggested Citation

  • Eric B. Gibbs & Feiyue Lu & Bede Portz & Michael J. Fisher & Brenda P. Medellin & Tatiana N. Laremore & Yan Jessie Zhang & David S. Gilmour & Scott A. Showalter, 2017. "Phosphorylation induces sequence-specific conformational switches in the RNA polymerase II C-terminal domain," Nature Communications, Nature, vol. 8(1), pages 1-11, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15233
    DOI: 10.1038/ncomms15233
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    Cited by:

    1. Robert Düster & Kanchan Anand & Sophie C. Binder & Maximilian Schmitz & Karl Gatterdam & Robert P. Fisher & Matthias Geyer, 2024. "Structural basis of Cdk7 activation by dual T-loop phosphorylation," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. David Flores-Solis & Irina P. Lushpinskaia & Anton A. Polyansky & Arya Changiarath & Marc Boehning & Milana Mirkovic & James Walshe & Lisa M. Pietrek & Patrick Cramer & Lukas S. Stelzl & Bojan Zagrovi, 2023. "Driving forces behind phase separation of the carboxy-terminal domain of RNA polymerase II," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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