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. Epub 2014 Jul 6.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Crystallography, X-Ray
  • HEK293 Cells
  • Humans
  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Sequence Data
  • Neoplasm Proteins / chemistry*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Multimerization
  • Protein Processing, Post-Translational*
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • RNA Polymerase II / chemistry*
  • RNA Polymerase II / metabolism
  • Repressor Proteins / chemistry*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Serine / chemistry

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • Neoplasm Proteins
  • RPAP2 protein, human
  • RPRD1A protein, human
  • RPRD1B protein, human
  • Repressor Proteins
  • Serine
  • RNA Polymerase II

Associated data

  • PDB/4FLA
  • PDB/4FLB
  • PDB/4JXT
  • PDB/4Q94
  • PDB/4Q96