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TitleRPAP2 regulates a transcription initiation checkpoint by inhibiting assembly of pre-initiation complex.
Journal, issue, pagesCell Rep, Vol. 39, Issue 4, Page 110732, Year 2022
Publish dateApr 26, 2022
AuthorsXinxin Wang / Yilun Qi / Zhenning Wang / Li Wang / Aixia Song / Bolin Tao / Jiabei Li / Dan Zhao / Hongwei Zhang / Qianwei Jin / Yi-Zhou Jiang / Fei Xavier Chen / Yanhui Xu / Xizi Chen /
PubMed AbstractRNA 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 ...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.
External linksCell Rep / PubMed:35476980
MethodsEM (single particle)
Resolution2.78 - 3.5 Å
Structure data

31450

7f4g

EMDB-31450, PDB-7f4g:
Structure of RPAP2-bound RNA polymerase II
Method: EM (single particle) / Resolution: 2.78 Å

EMDB-31451:
Structure of RPAP2-bound RNA Polymerase II
Method: EM (single particle) / Resolution: 3.5 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
  • sus scrofa (pig)
  • Pig (pig)
KeywordsTRANSCRIPTION / RPAP2 / RNA Polymerase II

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