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

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

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


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.

Original languageEnglish (US)
Article number15233
JournalNature communications
StatePublished - May 12 2017

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


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