U2 snRNA 3'-end processing / regulation of fertilization / NELF complex / meiotic spindle elongation / Integration of energy metabolism / NTRK3 as a dependence receptor / PP2A-mediated dephosphorylation of key metabolic factors / snRNA 3'-end processing / RNA polymerase II CTD heptapeptide repeat S2 phosphatase activity / RNA polymerase II CTD heptapeptide repeat S7 phosphatase activity ...U2 snRNA 3'-end processing / regulation of fertilization / NELF complex / meiotic spindle elongation / Integration of energy metabolism / NTRK3 as a dependence receptor / PP2A-mediated dephosphorylation of key metabolic factors / snRNA 3'-end processing / RNA polymerase II CTD heptapeptide repeat S2 phosphatase activity / RNA polymerase II CTD heptapeptide repeat S7 phosphatase activity / mitotic sister chromatid separation / MASTL Facilitates Mitotic Progression / negative regulation of DNA-templated transcription, elongation / protein phosphatase type 2A complex / protein serine/threonine phosphatase complex / regulation of meiotic cell cycle process involved in oocyte maturation / peptidyl-threonine dephosphorylation / meiotic sister chromatid cohesion, centromeric / snRNA processing / INTAC complex / RNA polymerase II CTD heptapeptide repeat S5 phosphatase activity / protein localization to nuclear envelope / FAR/SIN/STRIPAK complex / Regulation of glycolysis by fructose 2,6-bisphosphate metabolism / DSIF complex / Inhibition of replication initiation of damaged DNA by RB1/E2F1 / female meiotic nuclear division / eye development / regulation of transcription elongation by RNA polymerase II / protein phosphatase regulator activity / GABA receptor binding / flagellated sperm motility / integrator complex / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / protein antigen binding / Formation of RNA Pol II elongation complex / Formation of the Early Elongation Complex / Transcriptional regulation by small RNAs / RNA Polymerase II Pre-transcription Events / TP53 Regulates Transcription of DNA Repair Genes / FGFR2 alternative splicing / RNA polymerase II transcribes snRNA genes / mRNA Capping / mRNA Splicing - Minor Pathway / Processing of Capped Intron-Containing Pre-mRNA / RNA Polymerase II Promoter Escape / RNA Polymerase II Transcription Pre-Initiation And Promoter Opening / RNA Polymerase II Transcription Initiation / RNA Polymerase II Transcription Elongation / RNA Polymerase II Transcription Initiation And Promoter Clearance / RNA Pol II CTD phosphorylation and interaction with CE / Estrogen-dependent gene expression / Formation of TC-NER Pre-Incision Complex / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / mRNA Splicing - Major Pathway / ERKs are inactivated / negative regulation of stem cell differentiation / Initiation of Nuclear Envelope (NE) Reformation / Hydrolases; Acting on ester bonds; Endoribonucleases producing 3'-phosphomonoesters / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / Beta-catenin phosphorylation cascade / Signaling by GSK3beta mutants / CTNNB1 S33 mutants aren't phosphorylated / CTNNB1 S37 mutants aren't phosphorylated / CTNNB1 S45 mutants aren't phosphorylated / CTNNB1 T41 mutants aren't phosphorylated / RNA polymerase II transcription initiation surveillance / nuclear lumen / Co-stimulation by CD28 / regulation of growth / positive regulation of DNA-templated transcription, elongation / Disassembly of the destruction complex and recruitment of AXIN to the membrane / Abortive elongation of HIV-1 transcript in the absence of Tat / centrosome localization / nucleosomal DNA binding / negative regulation of epithelial to mesenchymal transition / inner cell mass cell proliferation / Co-inhibition by CTLA4 / Platelet sensitization by LDL / protein-serine/threonine phosphatase / transcription elongation-coupled chromatin remodeling / RNA Pol II CTD phosphorylation and interaction with CE during HIV infection / RNA Pol II CTD phosphorylation and interaction with CE / negative regulation of glycolytic process through fructose-6-phosphate / Formation of the Early Elongation Complex / Formation of the HIV-1 Early Elongation Complex / mRNA Capping / positive regulation of NLRP3 inflammasome complex assembly / ERK/MAPK targets / mesoderm development / protein serine/threonine phosphatase activity / vascular endothelial cell response to oscillatory fluid shear stress / T cell homeostasis / regulation of cell differentiation / regulation of G1/S transition of mitotic cell cycle / regulation of microtubule polymerization / maintenance of transcriptional fidelity during transcription elongation by RNA polymerase II Similarity search - Function
Journal: Nature / Year: 2024 Title: Structural basis of Integrator-dependent RNA polymerase II termination. Authors: Isaac Fianu / Moritz Ochmann / James L Walshe / Olexandr Dybkov / Joseph Neos Cruz / Henning Urlaub / Patrick Cramer / Abstract: 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.
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Homo sapiens (human) / 
Sus scrofa (pig) / 
Trichoplusia ni (cabbage looper) / synthetic construct (others)
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Germany, European Union, 3 items 
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Escherichia coli (E. coli)
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