Crosstalk between RNA Pol II C-Terminal Domain Acetylation and Phosphorylation via RPRD Proteins

Ali, I.; Garrido-Ruiz, D.; Ni, Z.; Johnson, J. R.; Zhang, H.; Li, P.-C.; Conrad, R. J.; Guo, X.; Min, J.; Greenblatt, J.; Jacobson, M.; Krogan, N. J.; Ott, M.

doi:10.1101/442491

bioRxiv · 10.1101/442491

Crosstalk between RNA Pol II C-Terminal Domain Acetylation and Phosphorylation via RPRD Proteins

Ali, I.·Garrido-Ruiz, D.·Ni, Z.·Johnson, J. R.·Zhang, H.·Li, P.-C.·Conrad, R. J.·Guo, X.·Min, J.·Greenblatt, J.·Jacobson, M.·Krogan, N. J.·Ott, M.

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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 RPRD proteins recruit K7 deacetylases, including HDAC1. We also report auto-regulatory crosstalk between K7ac and S5p via RPRD proteins and their interactions with acetyl- and phospho-eraser proteins.

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Ali, I., Garrido-Ruiz, D., Ni, Z., Johnson, J. R., Zhang, H., Li, P.-C., Conrad, R. J., Guo, X., Min, J., Greenblatt, J., Jacobson, M., Krogan, N. J., Ott, M.. 2018-10-26. Crosstalk between RNA Pol II C-Terminal Domain Acetylation and Phosphorylation via RPRD Proteins. https://doi.org/10.1101/442491

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