%0 Journal Article
%T RPAP2 regulates a transcription initiation checkpoint by inhibiting assembly of pre-initiation complex.
%A Wang X
%A Qi Y
%A Wang Z
%A Wang L
%A Song A
%A Tao B
%A Li J
%A Zhao D
%A Zhang H
%A Jin Q
%A Jiang YZ
%A Chen FX
%A Xu Y
%A Chen X
%J Cell Rep
%V 39
%N 4
%D 04 2022 26
%M 35476980
暂无%R 10.1016/j.celrep.2022.110732
%X RNA polymerase II (Pol II)-mediated transcription in metazoans requires precise regulation. RNA Pol II-associated protein 2 (RPAP2) was previously identified to transport Pol II from cytoplasm to nucleus and dephosphorylates Pol II C-terminal domain (CTD). Here, we show that RPAP2 binds hypo-/hyper-phosphorylated Pol II with undetectable phosphatase activity. The 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 and disrupts Pol II-TFIIF interaction and impairs in vitro transcription initiation, suggesting a function in inhibiting PIC assembly. Loss of RPAP2 in cells leads to global accumulation of TFIIF and Pol II at promoters, indicating a critical role of RPAP2 in inhibiting PIC assembly independent of its putative phosphatase activity. Our study indicates that RPAP2 functions as a gatekeeper to inhibit PIC assembly and transcription initiation and suggests a transcription checkpoint.