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

Priyanka Sharma, Antonios Lioutas, Narcis Fernandez-Fuentes, Javier Quilez, José Carbonell-Caballero, Roni H. G. Wright, Chiara Di Vona, François Le Dily, Roland Schüller, Dirk Eick, Baldomero Oliva

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43 Citations (SciVal)
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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
Original languageEnglish
Pages (from-to)84-96.e7
Number of pages13
JournalMolecular Cell
Volume73
Issue number1
Early online date21 Nov 2018
DOIs
Publication statusPublished - 03 Jan 2019

Keywords

  • RNA polymerase II CTD
  • citrullination
  • PADI2
  • arginine 1810
  • breast cancer cells
  • proximal promoter pausing
  • cell proliferation
  • P_TEFb complex
  • P-TEFb complex
  • arginine1810
  • Protein-Arginine Deiminases/genetics
  • Cell Proliferation
  • Humans
  • Protein-Arginine Deiminase Type 2
  • Gene Expression Regulation, Neoplastic
  • Arginine
  • MCF-7 Cells
  • Breast Neoplasms/enzymology
  • Protein Domains
  • Female
  • Transcription, Genetic
  • Citrullination
  • Promoter Regions, Genetic
  • Signal Transduction
  • RNA Polymerase II/chemistry
  • Gene Expression Regulation, Enzymologic
  • Positive Transcriptional Elongation Factor B/genetics
  • Protein Binding
  • Protein Processing, Post-Translational

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