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Structure paper

タイトル	Structural basis of Integrator-dependent RNA polymerase II termination.
ジャーナル・号・ページ	Nature, Vol. 629, Issue 8010, Page 219-227, Year 2024
掲載日	2024年4月3日
著者	Isaac Fianu / Moritz Ochmann / James L Walshe / Olexandr Dybkov / Joseph Neos Cruz / Henning Urlaub / Patrick Cramer /
PubMed 要旨	The Integrator complex can terminate RNA polymerase II (Pol II) in the promoter-proximal region of genes. Previous work has shed light on how Integrator binds to the paused elongation complex ...The Integrator complex can terminate RNA polymerase II (Pol II) in the promoter-proximal region of genes. Previous work has shed light on how Integrator binds to the paused elongation complex consisting of Pol II, the DRB sensitivity-inducing factor (DSIF) and the negative elongation factor (NELF) and how it cleaves the nascent RNA transcript, but has not explained how Integrator removes Pol II from the DNA template. Here we present three cryo-electron microscopy structures of the complete Integrator-PP2A complex in different functional states. The structure of the pre-termination complex reveals a previously unresolved, scorpion-tail-shaped INTS10-INTS13-INTS14-INTS15 module that may use its 'sting' to open the DSIF DNA clamp and facilitate termination. The structure of the post-termination complex shows that the previously unresolved subunit INTS3 and associated sensor of single-stranded DNA complex (SOSS) factors prevent Pol II rebinding to Integrator after termination. The structure of the free Integrator-PP2A complex in an inactive closed conformation reveals that INTS6 blocks the PP2A phosphatase active site. These results lead to a model for how Integrator terminates Pol II transcription in three steps that involve major rearrangements.
リンク	Nature / PubMed:38570683 / PubMed Central
手法	EM (単粒子)
解像度	3.1 - 4.1 Å
構造データ	19038 8rbx EMDB-19038, PDB-8rbx: Structure of Integrator-PP2A bound to a paused RNA polymerase II-DSIF-NELF-nucleosome complex 手法: EM (単粒子) / 解像度: 4.1 Å 19040 8rbz EMDB-19040, PDB-8rbz: Structure of Integrator-PP2A-SOSS-CTD post-termination complex 手法: EM (単粒子) / 解像度: 3.7 Å 19047 8rc4 EMDB-19047, PDB-8rc4: Structure of Integrator-PP2A complex 手法: EM (単粒子) / 解像度: 3.1 Å
化合物	ChemComp-ZN: Unknown entry ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-MN: Unknown entry
由来	homo sapiens (ヒト) sus scrofa (ブタ) trichoplusia ni (イラクサキンウワバ) synthetic construct (人工物)
キーワード	TRANSCRIPTION (転写 (生物学)) / Integrator complex (積分器) / Pre-termination complex / Post-termination complex / RNA Polymerase II (RNAポリメラーゼII) / Pol II / RNAPII