- EMDB-54251: Activated Elongation Complex with IWS1 and ELOF1 -
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Basic information
Entry
Database: EMDB / ID: EMD-54251
Title
Activated Elongation Complex with IWS1 and ELOF1
Map data
Sample
Complex: Activated Elongation Complex (ECstar) with IWS1 and ELOF1
Protein or peptide: x 22 types
DNA: x 2 types
RNA: x 1 types
Ligand: x 2 types
Keywords
RNA Pol II / Elongation / TRANSCRIPTION
Function / homology
Function and homology information
blastocyst growth / Ski complex / RNA polymerase II C-terminal domain phosphoserine binding / mRNA decay by 3' to 5' exoribonuclease / Cdc73/Paf1 complex / positive regulation of mRNA 3'-end processing / inner cell mass cell differentiation / regulation of mRNA export from nucleus / regulation of isotype switching / nuclear-transcribed mRNA catabolic process, 3'-5' exonucleolytic nonsense-mediated decay ...blastocyst growth / Ski complex / RNA polymerase II C-terminal domain phosphoserine binding / mRNA decay by 3' to 5' exoribonuclease / Cdc73/Paf1 complex / positive regulation of mRNA 3'-end processing / inner cell mass cell differentiation / regulation of mRNA export from nucleus / regulation of isotype switching / nuclear-transcribed mRNA catabolic process, 3'-5' exonucleolytic nonsense-mediated decay / negative regulation of DNA-templated transcription, elongation / regulation of muscle cell differentiation / endodermal cell fate commitment / negative regulation of myeloid cell differentiation / positive regulation of cell cycle G1/S phase transition / DSIF complex / regulation of mRNA processing / trophectodermal cell differentiation / regulation of transcription elongation by RNA polymerase II / blastocyst hatching / nucleosome organization / 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 / blastocyst formation / nuclear lumen / mRNA 3'-end processing / positive regulation of DNA-templated transcription, elongation / Abortive elongation of HIV-1 transcript in the absence of Tat / poly(A)+ mRNA export from nucleus / stem cell population maintenance / interleukin-6-mediated signaling pathway / negative regulation of G1/S transition of mitotic cell cycle / RNA Pol II CTD phosphorylation and interaction with CE during HIV infection / RNA Pol II CTD phosphorylation and interaction with CE / negative regulation of gene expression, epigenetic / transcription elongation-coupled chromatin remodeling / Formation of the Early Elongation Complex / Formation of the HIV-1 Early Elongation Complex / mRNA Capping / RNA polymerase II complex binding / maintenance of transcriptional fidelity during transcription elongation by RNA polymerase II / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / negative regulation of transcription elongation by RNA polymerase II / positive regulation of macroautophagy / RNA polymerase II transcribes snRNA genes / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / positive regulation of Wnt signaling pathway / protein localization to nucleus / cell surface receptor signaling pathway via JAK-STAT / mRNA transport / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / RNA polymerase I complex / transcription elongation by RNA polymerase I / RNA polymerase III complex / Formation of HIV elongation complex in the absence of HIV Tat / negative regulation of fibroblast proliferation / RNA polymerase II, core complex / tRNA transcription by RNA polymerase III / nucleosome binding / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / translation initiation factor binding / transcription-coupled nucleotide-excision repair / RNA Polymerase II Pre-transcription Events / DNA-directed RNA polymerase complex / rescue of stalled ribosome / SH2 domain binding / RNA splicing / transcription elongation factor complex / Hedgehog 'on' state / TP53 Regulates Transcription of DNA Repair Genes / transcription initiation at RNA polymerase II promoter / transcription elongation by RNA polymerase II / DNA-templated transcription initiation / regulation of cell growth / positive regulation of transcription elongation by RNA polymerase II / Formation of the beta-catenin:TCF transactivating complex / euchromatin Similarity search - Function
DNA-directed RNA polymerase II subunit RPB4 / DNA-directed RNA polymerase subunit / DNA-directed RNA polymerases I, II, and III subunit RPABC5 / DNA-directed RNA polymerases I, II, and III subunit RPABC4 / DNA-directed RNA polymerase subunit / 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 RPB4 / DNA-directed RNA polymerase subunit / DNA-directed RNA polymerases I, II, and III subunit RPABC5 / DNA-directed RNA polymerases I, II, and III subunit RPABC4 / DNA-directed RNA polymerase subunit / 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 polymerases I, II, and III subunit RPABC1 / Transcription elongation factor SPT5 / Transcription elongation factor 1 homolog / DNA-directed RNA polymerase II subunit RPB9 / Transcription elongation factor SPT4 / Parafibromin / RNA polymerase-associated protein CTR9 homolog / Transcription elongation factor SPT6 / RNA polymerase II-associated factor 1 homolog / RNA polymerase-associated protein LEO1 / Protein IWS1 homolog / Superkiller complex protein 8 Similarity search - Component
Biological species
Homo sapiens (human) / Sus scrofa (pig) / synthetic construct (others)
Method
single particle reconstruction / cryo EM / Resolution: 4.01 Å
Journal: Nat Commun / Year: 2025 Title: IWS1 positions downstream DNA to globally stimulate Pol II elongation. Authors: Aiturgan Zheenbekova / James L Walshe / Moritz Ochmann / Moritz Bäuerle / Ute Neef / Kerstin C Maier / Petra Rus / Yumeng Yan / Henning Urlaub / Patrick Cramer / Kristina Žumer / Abstract: The protein IWS1 (Interacts with SPT6 1) is implicated in transcription-associated processes, but a direct role in RNA polymerase (Pol) II function is unknown. Here, we use multi-omics kinetic ...The protein IWS1 (Interacts with SPT6 1) is implicated in transcription-associated processes, but a direct role in RNA polymerase (Pol) II function is unknown. Here, we use multi-omics kinetic analysis after rapid depletion of IWS1 in human cells to show that loss of IWS1 results in a global decrease of RNA synthesis and a global reduction in Pol II elongation velocity. We then resolve the cryo-EM structure of the activated Pol II elongation complex with bound IWS1 and elongation factor ELOF1 and show that IWS1 acts as a scaffold and positions downstream DNA within the cleft of Pol II. In vitro assays show that the disordered C-terminal region of IWS1 that contacts the cleft of Pol II is responsible for stimulation of Pol II activity and is aided by ELOF1. Finally, we find that the defect in transcription upon IWS1 depletion leads to a decrease of histone H3 tri-methylation at residue lysine-36 (H3K36me3), but that this secondary effect is an indirect function of IWS1. In summary, our structure-function analysis establishes IWS1 as a Pol II-associated elongation factor that acts globally to stimulate Pol II elongation velocity and ensure proper co-transcriptional histone methylation.
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