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Structural heterogeneity in the intrinsically disordered RNA polymerase II C-terminal domain

Author

Listed:
  • Bede Portz

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

  • Feiyue Lu

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

  • Eric B. Gibbs

    (The Pennsylvania State University)

  • Joshua E. Mayfield

    (University of Texas)

  • M. Rachel Mehaffey

    (University of Texas)

  • Yan Jessie Zhang

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

  • Jennifer S. Brodbelt

    (University of Texas)

  • Scott A. Showalter

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

  • David S. Gilmour

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

Abstract

RNA polymerase II contains a repetitive, intrinsically disordered, C-terminal domain (CTD) composed of heptads of the consensus sequence YSPTSPS. The CTD is heavily phosphorylated and serves as a scaffold, interacting with factors involved in transcription initiation, elongation and termination, RNA processing and chromatin modification. Despite being a nexus of eukaryotic gene regulation, the structure of the CTD and the structural implications of phosphorylation are poorly understood. Here we present a biophysical and biochemical interrogation of the structure of the full length CTD of Drosophila melanogaster, which we conclude is a compact random coil. Surprisingly, we find that the repetitive CTD is structurally heterogeneous. Phosphorylation causes increases in radius, protein accessibility and stiffness, without disrupting local structural heterogeneity. Additionally, we show the human CTD is also structurally heterogeneous and able to substitute for the D. melanogaster CTD in supporting fly development to adulthood. This finding implicates conserved structural organization, not a precise array of heptad motifs, as important to CTD function.

Suggested Citation

  • Bede Portz & Feiyue Lu & Eric B. Gibbs & Joshua E. Mayfield & M. Rachel Mehaffey & Yan Jessie Zhang & Jennifer S. Brodbelt & Scott A. Showalter & David S. Gilmour, 2017. "Structural heterogeneity in the intrinsically disordered RNA polymerase II C-terminal domain," Nature Communications, Nature, vol. 8(1), pages 1-12, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15231
    DOI: 10.1038/ncomms15231
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    Cited by:

    1. 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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