Entry Database : EMDB / ID : EMD-19038 Downloads & linksTitle Structure of Integrator-PP2A bound to a paused RNA polymerase II-DSIF-NELF-nucleosome complex Map dataOverall map filtered by local resolution Details SampleComplex : Pre-termination complexComplex : Integrator-PP2A complex and NELFProtein or peptide : x 19 typesComplex : NucleosomeProtein or peptide : x 5 typesComplex : RNA and DNADNA : x 2 typesRNA : x 1 typesComplex : DNA-directed RNA Polymerase IIProtein or peptide : x 13 typesComplex : DSIFProtein or peptide : x 1 typesLigand : x 3 types Details Keywords Integrator complex / Pre-termination complex / TRANSCRIPTIONFunction / homology Function and homology informationFunction Domain/homology Component
U2 snRNA 3'-end processing / regulation of fertilization / NELF complex / meiotic spindle elongation / Integration of energy metabolism / PP2A-mediated dephosphorylation of key metabolic factors / NTRK3 as a dependence receptor / snRNA 3'-end processing / MASTL Facilitates Mitotic Progression / regulation of meiotic cell cycle process involved in oocyte maturation ... U2 snRNA 3'-end processing / regulation of fertilization / NELF complex / meiotic spindle elongation / Integration of energy metabolism / PP2A-mediated dephosphorylation of key metabolic factors / NTRK3 as a dependence receptor / snRNA 3'-end processing / MASTL Facilitates Mitotic Progression / regulation of meiotic cell cycle process involved in oocyte maturation / mitotic sister chromatid separation / negative regulation of DNA-templated transcription, elongation / protein phosphatase type 2A complex / protein serine/threonine phosphatase complex / peptidyl-threonine dephosphorylation / meiotic sister chromatid cohesion, centromeric / snRNA processing / peptidyl-serine dephosphorylation / FAR/SIN/STRIPAK complex / protein localization to nuclear envelope / : / Regulation of glycolysis by fructose 2,6-bisphosphate metabolism / female meiotic nuclear division / DSIF complex / Inhibition of replication initiation of damaged DNA by RB1/E2F1 / regulation of transcription elongation by RNA polymerase II / protein antigen binding / GABA receptor binding / protein phosphatase regulator activity / flagellated sperm motility / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / integrator complex / 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 / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / ERKs are inactivated / Initiation of Nuclear Envelope (NE) Reformation / negative regulation of stem cell differentiation / 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 / Hydrolases; Acting on ester bonds; Endoribonucleases producing 3'-phosphomonoesters / 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 / negative regulation of epithelial to mesenchymal transition / nucleosomal DNA binding / inner cell mass cell proliferation / Co-inhibition by CTLA4 / protein serine/threonine phosphatase activity / transcription elongation-coupled chromatin remodeling / Platelet sensitization by LDL / histone H2AXS140 phosphatase activity / RNA polymerase II CTD heptapeptide repeat Y1 phosphatase activity / RNA polymerase II CTD heptapeptide repeat T4 phosphatase activity / RNA polymerase II CTD heptapeptide repeat S2 phosphatase activity / RNA polymerase II CTD heptapeptide repeat S5 phosphatase activity / RNA polymerase II CTD heptapeptide repeat S7 phosphatase activity / MAP kinase serine/threonine phosphatase activity / calmodulin-dependent protein phosphatase activity / myosin phosphatase activity / protein-serine/threonine phosphatase / 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 / positive regulation of NLRP3 inflammasome complex assembly / Formation of the Early Elongation Complex / Formation of the HIV-1 Early Elongation Complex / mRNA Capping / ERK/MAPK targets / T cell homeostasis / mesoderm development Similarity search - Function Domain of unknown function DUF3677 / Integrator complex subunit 2, metazoa / Integrator complex subunit 2 / Integrator complex subunit 7 / Integrator complex subunit 1 / : / : / : / : / : ... Domain of unknown function DUF3677 / Integrator complex subunit 2, metazoa / Integrator complex subunit 2 / Integrator complex subunit 7 / Integrator complex subunit 1 / : / : / : / : / : / : / Integrator complex subunit 1, RP2B-binding domain / Integrator complex subunit 2 / Integrator complex subunit 1, R3 domain / Integrator complex subunit 1, R4 domain / Integrator complex subunit 1, INTS2-binding domain / Integrator complex subunit 7, C-terminal domain / Integrator complex subunit 7, N-terminal / Integrator complex subunit 7 helical bundle / Integrator complex subunit 10 / Integrator complex subunit 15 / INTS6/SAGE1/DDX26B/CT45, C-terminal / Integrator complex subunit 14 / Integrator complex subunit 14, beta-barrel domain / Integrator complex subunit 14, C-terminal / : / Integrator complex subunit 15 / INTS6/SAGE1/DDX26B/CT45 C-terminus / Integrator complex subunit 14, beta-barrel domain / Integrator complex subunit 14, alpha-helical domain / Integrator subunit 10 / Cell cycle regulator Mat89Bb / Cell cycle and development regulator Mat89Bb / Integrator complex subunit 5, C-terminal / Integrator complex subunit 5, N-terminal / Integrator complex subunit 8 / Integrator complex subunit 5 / Integrator complex subunit 5 N-terminus / Integrator complex subunit 5 C-terminus / : / INTS4 8 helical bundle domain / Cofactor of BRCA1 / Cofactor of BRCA1 (COBRA1) / : / NELF-A N-terminal domain / TH1 protein / TH1 protein / Sister chromatid cohesion protein PDS5 protein / Integrator complex subunit 9 / Hepatitis delta antigen (HDAg) domain / : / Integrator IntS9, C-terminal domain / Hepatitis delta antigen (HDAg) domain profile. / Integrator complex subunit 11, MBL-fold / : / Integrator IntS11, C-terminal domain / : / Metallo-beta-lactamase superfamily domain / : / : / Beta-Casp domain / Beta-Casp domain / Beta-Casp domain / Spt5, KOW domain repeat 6 / Transcription elongation factor SPT5, seventh KOW domain / Transcription elongation factor SPT5, sixth KOW domain / Zn-dependent metallo-hydrolase, RNA specificity domain / Zn-dependent metallo-hydrolase RNA specificity domain / Transcription elongation factor SPT5, KOWx domain / Transcription elongation factor SPT5, KOW1 domain / Transcription elongation factor SPT5, second KOW domain / Transcription elongation factor SPT5, fifth KOW domain / Transcription elongation factor SPT5, fourth KOW domain / HEAT repeat / Transcription elongation factor Spt5, eukaryote / Spt5 transcription elongation factor, N-terminal / Spt5, KOW domain repeat 2 / Spt5, KOW domain repeat 3 / Spt5, KOW domain repeat 5 / Spt5 transcription elongation factor, acidic N-terminal / NGN domain, eukaryotic / Spt5, KOW domain repeat 1 / Spt5, KOW domain repeat 4 / HEAT repeat / Spt5 C-terminal domain / Spt5 C-terminal nonapeptide repeat binding Spt4 / NGN domain / Transcription elongation factor SPT5 / Early transcription elongation factor of RNA pol II, NGN section / : / PPP2R1A-like HEAT repeat / Serine/threonine specific protein phosphatases signature. / Protein phosphatase 2A homologues, catalytic domain. / Serine/threonine-specific protein phosphatase/bis(5-nucleosyl)-tetraphosphatase / HEAT repeat profile. / HEAT, type 2 / von Willebrand factor type A domain / HEAT repeats / NusG, N-terminal / In Spt5p, this domain may confer affinity for Spt4p. It possesses a RNP-like fold. Similarity search - Domain/homology RNA polymerase II subunit D / DNA-directed RNA polymerase subunit / DNA-directed RNA polymerases I, II, and III subunit RPABC5 / DNA-directed RNA polymerase subunit / RNA polymerase II subunit K / DNA-directed RNA polymerases I, II, and III subunit RPABC2 / DNA-directed RNA polymerase II subunit RPB11-a / DNA-directed RNA polymerases I, II, and III subunit RPABC3 / DNA-directed RNA polymerase II subunit RPB3 / DNA-directed RNA polymerase subunit beta ... RNA polymerase II subunit D / DNA-directed RNA polymerase subunit / DNA-directed RNA polymerases I, II, and III subunit RPABC5 / DNA-directed RNA polymerase subunit / RNA polymerase II subunit K / DNA-directed RNA polymerases I, II, and III subunit RPABC2 / DNA-directed RNA polymerase II subunit RPB11-a / DNA-directed RNA polymerases I, II, and III subunit RPABC3 / DNA-directed RNA polymerase II subunit RPB3 / DNA-directed RNA polymerase subunit beta / DNA-directed RNA polymerase II subunit E / Transcription elongation factor SPT5 / Histone H2A type 1 / Histone H2B type 1-J / Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform / DNA-directed RNA polymerase II subunit RPB9 / Histone H4 / Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform / Integrator complex subunit 11 / Histone H3.3C / Integrator complex subunit 5 / Integrator complex subunit 8 / Negative elongation factor C/D / Integrator complex subunit 1 / Negative elongation factor B / Integrator complex subunit 4 / Integrator complex subunit 15 / Integrator complex subunit 14 / Integrator complex subunit 2 / Negative elongation factor A / Integrator complex subunit 9 / Integrator complex subunit 7 / Integrator complex subunit 13 / Integrator complex subunit 10 / Integrator complex subunit 6 Similarity search - ComponentBiological species Homo sapiens (human) / Sus scrofa (pig) / Trichoplusia ni (cabbage looper) / synthetic construct (others) Method single particle reconstruction / cryo EM / Resolution : 4.1 Å Details AuthorsFianu I / Ochmann M / Walshe JL / Cramer P Funding support Germany, European Union, 3 items Details Hide detailsOrganization Grant number Country German Research Foundation (DFG) SFB860 Germany German Research Foundation (DFG) SFB1565 Germany European Research Council (ERC) EXC 2067/1-390729940 European Union
CitationJournal : Nature / Year : 2024Title : 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. History Deposition Dec 5, 2023 - Header (metadata) release Feb 7, 2024 - Map release Feb 7, 2024 - Update May 15, 2024 - Current status May 15, 2024 Processing site : PDBe / Status : Released
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