The Relation between RPRD1A and H3-T45 Phosphorylation in Transcriptional Termination of DNA Damage Response Gene

Abstract

Core histones undergo diverse post-translational modifications to regulate the transcription process. On our previous report, we showed that AKT1 phosphorylates 45th threonine of histone H3 (H3T45) under DNA damage conditions. It enhances transcription by facilitating transcriptional termination. However, the precise mechanism of phosphorylated H3T45 (p-H3T45) -enhanced transcriptional termination is not yet understood. In this study, we show that human orthologs of yeast transcription termination factor Rtt103, RPRD1A and RPRD1B, interact with AKT1. RPRD1A, not RPRD1B, harbors well-conserved AKT phosphorylation site on its carboxy-terminal coiled-coil structure (Serine 285). Under the DNA damage conditions, RPRD1A knockdown had no effect on H3T45 phosphorylation, but caused impaired CDKN1A transcriptional induction. AKT1 mediated phosphorylation of H3T45 and RPRD1A-S285 both increased their binding affinity. Finally, S285A mutation impaired RNA polymerase II (Pol II) dissociation from the chromatin, resulting improper transcriptional termination and reduced transcription efficiency. Taken together, we suggest a novel mechanistic insight that RPRD1A transmits H3T45 phosphorylation signal to transcriptional termination.