1. Crosstalk between RNA Pol II C-Terminal Domain Acetylation and Phosphorylation via RPRD Proteins
- Author
-
Ali, Ibraheem, Ruiz, Diego Garrido, Ni, Zuyao, Johnson, Jeffrey R, Zhang, Heng, Li, Pao-Chen, Khalid, Mir M, Conrad, Ryan J, Guo, Xinghua, Min, Jinrong, Greenblatt, Jack, Jacobson, Matthew, Krogan, Nevan J, and Ott, Melanie
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Genetics ,Underpinning research ,1.1 Normal biological development and functioning ,Generic health relevance ,Acetylation ,Amino Acid Sequence ,Animals ,Binding Sites ,Cell Cycle Proteins ,HEK293 Cells ,Humans ,Mice ,Models ,Molecular ,NIH 3T3 Cells ,Neoplasm Proteins ,Phosphorylation ,Protein Binding ,Protein Conformation ,alpha-Helical ,Protein Conformation ,beta-Strand ,Protein Interaction Domains and Motifs ,Protein Isoforms ,Protein Processing ,Post-Translational ,RNA Polymerase II ,RNA ,Small Interfering ,Sequence Alignment ,Sequence Homology ,Amino Acid ,Thermodynamics ,C-terminal domain ,Pol II CTD ,RNA polymerase II ,acetylation ,crosstalk ,gene regulation ,histone deacetylase ,phosphorylation ,post-translational modification ,transcription ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Post-translational modifications of the RNA polymerase II C-terminal domain (CTD) coordinate the transcription cycle. Crosstalk between different modifications is poorly understood. Here, we show how acetylation of lysine residues at position 7 of characteristic heptad repeats (K7ac)-only found in higher eukaryotes-regulates phosphorylation of serines at position 5 (S5p), a conserved mark of polymerases initiating transcription. We identified the regulator of pre-mRNA-domain-containing (RPRD) proteins as reader proteins of K7ac. K7ac enhanced CTD peptide binding to the CTD-interacting domain (CID) of RPRD1A and RPRD1B proteins in isothermal calorimetry and molecular modeling experiments. Deacetylase inhibitors increased K7ac- and decreased S5-phosphorylated polymerases, consistent with acetylation-dependent S5 dephosphorylation by an RPRD-associated S5 phosphatase. Consistent with this model, RPRD1B knockdown increased S5p but enhanced K7ac, indicating that RPRD proteins recruit K7 deacetylases, including HDAC1. We also report autoregulatory crosstalk between K7ac and S5p via RPRD proteins and their interactions with acetyl- and phospho-eraser proteins.
- Published
- 2019