title: RPRD1A and RPRD1B are human RNA polymerase II C-terminal domain scaffolds for Ser5 dephosphorylation.
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.
authors.affiliation: Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Zuyao
authors.initials: Z
authors.lastname: Ni
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Chao
authors.initials: C
authors.lastname: Xu
authors.affiliation: Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Gerald O
authors.initials: GO
authors.lastname: Hunter
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Kuznetsova
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Tempel
authors.affiliation: Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Edyta
authors.initials: E
authors.lastname: Marcon
authors.affiliation: Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zhong
authors.affiliation: Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Wei-Hung William
authors.initials: WW
authors.lastname: Kuo
authors.affiliation: Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Joyce
authors.initials: J
authors.lastname: Li
authors.affiliation: Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Young
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Olsen
authors.affiliation: Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Cuihong
authors.initials: C
authors.lastname: Wan
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Loppnau
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Majida
authors.initials: M
authors.lastname: El Bakkouri
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Guillermo A
authors.initials: GA
authors.lastname: Senisterra
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Hao
authors.initials: H
authors.lastname: He
authors.affiliation: Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Haiming
authors.initials: H
authors.lastname: Huang
authors.affiliation: Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sachdev S
authors.initials: SS
authors.lastname: Sidhu
authors.affiliation: Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Emili
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
authors.forename: Shona
authors.initials: S
authors.lastname: Murphy
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Amber L
authors.initials: AL
authors.lastname: Mosley
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada.|Department of Medical Biophysics, University of Toronto, Ontario Cancer Institute, Campbell Family Cancer Research Institute, Toronto, Ontario, Canada.
authors.forename: Cheryl H
authors.initials: CH
authors.lastname: Arrowsmith
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada.|Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jinrong
authors.initials: J
authors.lastname: Min
authors.affiliation: Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jack F
authors.initials: JF
authors.lastname: Greenblatt
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D057809:HEK293 Cells; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D012319:RNA Polymerase II / Q000737:chemistry* / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000737:chemistry
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; C571028:RPAP2 protein, human; C470426:RPRD1A protein, human; C571225:RPRD1B protein, human; D012097:Repressor Proteins; D012694:Serine; D012319:RNA Polymerase II