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

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

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


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.

Original languageEnglish (US)
Article number15231
JournalNature communications
StatePublished - May 12 2017

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


Dive into the research topics of 'Structural heterogeneity in the intrinsically disordered RNA polymerase II C-terminal domain'. Together they form a unique fingerprint.

Cite this