TY - JOUR T1 - RPAP2 regulates a transcription initiation checkpoint by prohibiting assembly of preinitiation complex JF - bioRxiv DO - 10.1101/2021.06.18.448918 SP - 2021.06.18.448918 AU - Xizi Chen AU - Yilun Qi AU - Xinxin Wang AU - Zhenning Wang AU - Li Wang AU - Aixia Song AU - Jiabei Li AU - Dan Zhao AU - Hongwei Zhang AU - Qianwei Jin AU - Fei Xavier Chen AU - Yanhui Xu Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/06/18/2021.06.18.448918.abstract N2 - RNA polymerase II (Pol II)-mediated transcription in metazoan requires precise regulation. RNA polymerase II-associated protein 2 (RPAP2) was previously identified to transport Pol II from cytoplasm to nucleus and dephosphorylates Pol II C-terminal domain (CTD). We found that RPAP2 binds hypo/hyper-phosphorylated Pol II with undetectable phosphatase activity. Structure of RPAP2-Pol II shows mutually exclusive assembly of RPAP2-Pol II and pre-initiation complex (PIC) due to three steric clashes. RPAP2 prevents/disrupts Pol II-TFIIF interaction and impairs in vitro transcription initiation, suggesting a function in prohibiting PIC assembly. Loss of RPAP2 in cells leads to global accumulation of TFIIF and Pol II at promoters, indicating critical role of RPAP2 in inhibiting PIC assembly independent of its putative phosphatase activity. Our study indicates that RPAP2 functions as a gatekeeper to prohibit PIC assembly and transcription initiation and suggests a novel transcription checkpoint.Competing Interest StatementThe authors have declared no competing interest. ER -