{Reference Type}: Journal Article
{Title}: RPAP2 regulates a transcription initiation checkpoint by inhibiting assembly of pre-initiation complex.
{Author}: Wang X;Qi Y;Wang Z;Wang L;Song A;Tao B;Li J;Zhao D;Zhang H;Jin Q;Jiang YZ;Chen FX;Xu Y;Chen X;
{Journal}: Cell Rep
{Volume}: 39
{Issue}: 4
{Year}: 04 2022 26
暂无{DOI}: 10.1016/j.celrep.2022.110732
{Abstract}: 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.