Arginine Citrullination at the C-Terminal Domain Controls RNA Polymerase II Transcription

Authors Organisations
  • Priyanka Sharma(Author)
    The Barcelona Institute of Science and Technology (BIST)
  • Antonios Lioutas(Author)
    The Barcelona Institute of Science and Technology (BIST)
  • Narcis Fernandez Fuentes(Author)
  • Javier Quilez(Author)
    The Barcelona Institute of Science and Technology (BIST)
  • José Carbonell-Caballero(Author)
    The Barcelona Institute of Science and Technology (BIST)
  • Roni H. G. Wright(Author)
    The Barcelona Institute of Science and Technology (BIST)
  • Chiara Di Vona(Author)
    The Barcelona Institute of Science and Technology (BIST)
  • François Le Dily(Author)
    The Barcelona Institute of Science and Technology (BIST)
  • Roland Schüller(Author)
    Helmholtz Center Munich
  • Dirk Eick(Author)
    Helmholtz Center Munich
  • Baldomero Oliva(Author)
    Universitat Pompeu Fabra
    Structural Bioinformatics Laboratory (GRIB-IMIM)
Type Article
Original languageEnglish
Pages (from-to)84-96
Number of pages13
JournalMolecular Cell
Volume73
Issue number1
Early online date21 Nov 2018
DOI
Publication statusPublished - 03 Jan 2019
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Abstract

The post-translational modification of key residues at the C-terminal domain of RNA polymerase II (RNAP2-CTD) coordinates transcription, splicing, and RNA processing by modulating its capacity to act as a landing platform for a variety of protein complexes. Here, we identify a new modification at the CTD, the deimination of arginine and its conversion to citrulline by peptidyl arginine deiminase 2 (PADI2), an enzyme that has been associated with several diseases, including cancer. We show that, among PADI family members, only PADI2 citrullinates R1810 (Cit1810) at repeat 31 of the CTD. Depletion of PADI2 or loss of R1810 results in accumulation of RNAP2 at transcription start sites, reduced gene expression, and inhibition of cell proliferation. Cit1810 is needed for interaction with the P-TEFb (positive transcription elongation factor b) kinase complex and for its recruitment to chromatin. In this way, CTD-Cit1810 favors RNAP2 pause release and efficient transcription in breast cancer cells

Keywords

  • RNA polymerase II CTD, citrullination, PADI2, arginine 1810, breast cancer cells, proximal promoter pausing, cell proliferation, P_TEFb complex