2. Academic Validation
  3. RPRD1A and RPRD1B are human RNA polymerase II C-terminal domain scaffolds for Ser5 dephosphorylation

RPRD1A and RPRD1B are human RNA polymerase II C-terminal domain scaffolds for Ser5 dephosphorylation

  • Nat Struct Mol Biol. 2014 Aug;21(8):686-695. doi: 10.1038/nsmb.2853.
Zuyao Ni # 1,  Chao Xu # 2,  Xinghua Guo 1,  Gerald O Hunter 3,  Olga V Kuznetsova 4,  Wolfram Tempel 2,  Edyta Marcon 1,  Guoqing Zhong 1,  Hongbo Guo 1,  Wei-Hung William Kuo 5,  Joyce Li 1 5,  Peter Young 1,  Jonathan B Olsen 5,  Cuihong Wan 1,  Peter Loppnau 2,  Majida El Bakkouri 2,  Guillermo A Senisterra 2,  Hao He 2,  Haiming Huang 1,  Sachdev S Sidhu 1 5,  Andrew Emili 1 5,  Shona Murphy 4,  Amber L Mosley 3,  Cheryl H Arrowsmith 2 6,  Jinrong Min 2 7,  Jack F Greenblatt 1 5
Affiliations

Affiliations

  • 1 Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
  • 2 Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada.
  • 3 Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • 4 Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
  • 5 Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
  • 6 Department of Medical Biophysics, University of Toronto, Ontario Cancer Institute, Campbell Family Cancer Research Institute, Toronto, Ontario, Canada.
  • 7 Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
  • # Contributed equally.
PMID: 24997600 DOI: 10.1038/nsmb.2853
Abstract

The RNA polymerase II (RNAPII) C-terminal domain (CTD) heptapeptide repeats (1-YSPTSPS-7) undergo dynamic phosphorylation and dephosphorylation during the transcription cycle to recruit factors that regulate transcription, RNA processing and chromatin modification. We show here that RPRD1A and RPRD1B form homodimers and heterodimers through their coiled-coil domains and interact preferentially via CTD-interaction domains (CIDs) with RNAPII CTD repeats phosphorylated at S2 and S7. Crystal structures of the RPRD1A, RPRD1B and RPRD2 CIDs, alone and in complex with RNAPII CTD phosphoisoforms, elucidate the molecular basis of CTD recognition. In an example of cross-talk between different CTD modifications, our data also indicate that RPRD1A and RPRD1B associate directly with RPAP2 Phosphatase and, by interacting with CTD repeats where phospho-S2 and/or phospho-S7 bracket a phospho-S5 residue, serve as CTD scaffolds to coordinate the dephosphorylation of phospho-S5 by RPAP2.

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