7F4G

Structure of RPAP2-bound RNA polymerase II

Summary for 7F4G

• Entry DOI: 10.2210/pdb7f4g/pdb
• EMDB information: 31450
• Descriptor: RPB1, RPB12, RPAP2, ... (14 entities in total)
• Functional Keywords: rpap2, rna polymerase ii, transcription
• Biological source: Homo sapiens; More
• Total number of polymer chains: 13
• Total formula weight: 587296.36

Authors

Chen, X.,Qi, Y.,Wang, X.,Li, J.,Zhao, D.,Xu, Y. (deposition date: 2021-06-18, release date: 2021-07-07, Last modification date: 2024-10-23)

Primary citation

Wang, X.,Qi, Y.,Wang, Z.,Wang, L.,Song, A.,Tao, B.,Li, J.,Zhao, D.,Zhang, H.,Jin, Q.,Jiang, Y.Z.,Chen, F.X.,Xu, Y.,Chen, X.
RPAP2 regulates a transcription initiation checkpoint by inhibiting assembly of pre-initiation complex.
Cell Rep, 39:110732-110732, 2022

PubMed 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.

PubMed: 35476980
DOI: 10.1016/j.celrep.2022.110732

Experimental method

ELECTRON MICROSCOPY (2.78 Å)