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- EMDB-19399: Integrative Structure of the human intron lariat Spliceosome (ILS'') -
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Open data
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Basic information
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Title | Integrative Structure of the human intron lariat Spliceosome (ILS'') | |||||||||
![]() | composite map | |||||||||
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![]() | mRNA / splicing / intron lariat spliceosome / pre-mRNA | |||||||||
Function / homology | ![]() RNA lariat debranching enzyme activator activity / spliceosomal complex disassembly / post-spliceosomal complex / biomineral tissue development / negative regulation of double-strand break repair via nonhomologous end joining / U2-type post-mRNA release spliceosomal complex / protection from non-homologous end joining at telomere / regulation of skeletal muscle satellite cell proliferation / regulation of retinoic acid receptor signaling pathway / positive regulation of myoblast proliferation ...RNA lariat debranching enzyme activator activity / spliceosomal complex disassembly / post-spliceosomal complex / biomineral tissue development / negative regulation of double-strand break repair via nonhomologous end joining / U2-type post-mRNA release spliceosomal complex / protection from non-homologous end joining at telomere / regulation of skeletal muscle satellite cell proliferation / regulation of retinoic acid receptor signaling pathway / positive regulation of myoblast proliferation / post-mRNA release spliceosomal complex / U2 snRNP binding / U7 snRNA binding / histone pre-mRNA DCP binding / 3'-5' RNA helicase activity / endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / U7 snRNP / generation of catalytic spliceosome for first transesterification step / histone methyltransferase binding / histone pre-mRNA 3'end processing complex / alternative mRNA splicing, via spliceosome / regulation of vitamin D receptor signaling pathway / SLBP independent Processing of Histone Pre-mRNAs / SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs / response to alkaloid / nuclear retinoic acid receptor binding / embryonic brain development / protein methylation / U12-type spliceosomal complex / oocyte development / 7-methylguanosine cap hypermethylation / RNA splicing, via transesterification reactions / U1 snRNP binding / mRNA 3'-end processing / sno(s)RNA-containing ribonucleoprotein complex / methylosome / ATP-dependent activity, acting on RNA / pICln-Sm protein complex / U2-type catalytic step 1 spliceosome / pre-mRNA binding / positive regulation of mRNA splicing, via spliceosome / snRNP binding / small nuclear ribonucleoprotein complex / SMN-Sm protein complex / P granule / host-mediated activation of viral transcription / spliceosomal tri-snRNP complex / U2-type precatalytic spliceosome / telomerase holoenzyme complex / U2-type spliceosomal complex / positive regulation of vitamin D receptor signaling pathway / telomerase RNA binding / commitment complex / mRNA cis splicing, via spliceosome / U2-type prespliceosome assembly / nuclear vitamin D receptor binding / Transport of Mature mRNA derived from an Intron-Containing Transcript / Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells / Notch binding / RUNX3 regulates NOTCH signaling / U2-type catalytic step 2 spliceosome / positive regulation of neurogenesis / NOTCH4 Intracellular Domain Regulates Transcription / U4 snRNP / U2 snRNP / RNA Polymerase II Transcription Termination / U1 snRNP / NOTCH3 Intracellular Domain Regulates Transcription / protein peptidyl-prolyl isomerization / U2-type prespliceosome / inner cell mass cell proliferation / WD40-repeat domain binding / ubiquitin-ubiquitin ligase activity / nuclear androgen receptor binding / K63-linked polyubiquitin modification-dependent protein binding / precatalytic spliceosome / snoRNA binding / muscle organ development / RNA polymerase II CTD heptapeptide repeat P3 isomerase activity / RNA polymerase II CTD heptapeptide repeat P6 isomerase activity / generation of catalytic spliceosome for second transesterification step / lipid biosynthetic process / Notch-HLH transcription pathway / Formation of paraxial mesoderm / SMAD binding / positive regulation of transforming growth factor beta receptor signaling pathway / spliceosomal complex assembly / mitotic G2 DNA damage checkpoint signaling / mRNA Splicing - Minor Pathway / mRNA 3'-splice site recognition / spliceosomal tri-snRNP complex assembly / Prp19 complex / blastocyst development / protein K63-linked ubiquitination / U5 snRNA binding / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / U5 snRNP / protein localization to nucleus / positive regulation of G1/S transition of mitotic cell cycle / embryonic organ development Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
![]() | Rothe P / Vorlaender MK / Plaschka C | |||||||||
Funding support | European Union, 1 items
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![]() | ![]() Title: Mechanism for the initiation of spliceosome disassembly. Authors: Matthias K Vorländer / Patricia Rothe / Justus Kleifeld / Eric D Cormack / Lalitha Veleti / Daria Riabov-Bassat / Laura Fin / Alex W Phillips / Luisa Cochella / Clemens Plaschka / ![]() ![]() Abstract: Precursor-mRNA (pre-mRNA) splicing requires the assembly, remodelling and disassembly of the multi-megadalton ribonucleoprotein complex called the spliceosome. Recent studies have shed light on ...Precursor-mRNA (pre-mRNA) splicing requires the assembly, remodelling and disassembly of the multi-megadalton ribonucleoprotein complex called the spliceosome. Recent studies have shed light on spliceosome assembly and remodelling for catalysis, but the mechanism of disassembly remains unclear. Here we report cryo-electron microscopy structures of nematode and human terminal intron lariat spliceosomes along with biochemical and genetic data. Our results uncover how four disassembly factors and the conserved RNA helicase DHX15 initiate spliceosome disassembly. The disassembly factors probe large inner and outer spliceosome surfaces to detect the release of ligated mRNA. Two of these factors, TFIP11 and C19L1, and three general spliceosome subunits, SYF1, SYF2 and SDE2, then dock and activate DHX15 on the catalytic U6 snRNA to initiate disassembly. U6 therefore controls both the start and end of pre-mRNA splicing. Taken together, our results explain the molecular basis of the initiation of canonical spliceosome disassembly and provide a framework to understand general spliceosomal RNA helicase control and the discard of aberrant spliceosomes. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 61.3 KB 61.3 KB | Display Display | ![]() |
Images | ![]() | 96.2 KB | ||
Filedesc metadata | ![]() | 18.7 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 374.7 KB | Display | ![]() |
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Full document | ![]() | 374.3 KB | Display | |
Data in XML | ![]() | 7.1 KB | Display | |
Data in CIF | ![]() | 8.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8ro2MC ![]() 8ro0C ![]() 8ro1C ![]() 9fmdC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||
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Annotation | composite map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.2375 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
+Entire : Human Intron-lariat splicoesome
+Supramolecule #1: Human Intron-lariat splicoesome
+Macromolecule #1: U2 snRNA
+Macromolecule #2: U6 snRNA
+Macromolecule #26: U5 snRNA
+Macromolecule #29: INTRON
+Macromolecule #3: 116 kDa U5 small nuclear ribonucleoprotein component
+Macromolecule #4: Pre-mRNA-splicing factor ISY1 homolog
+Macromolecule #5: ATP-dependent RNA helicase DHX15
+Macromolecule #6: U5 small nuclear ribonucleoprotein 40 kDa protein
+Macromolecule #7: Crooked neck-like protein 1
+Macromolecule #8: Pre-mRNA-splicing factor SPF27
+Macromolecule #9: CWF19-like protein 1
+Macromolecule #10: Protein BUD31 homolog
+Macromolecule #11: Pre-mRNA-splicing factor RBM22
+Macromolecule #12: Intron-binding protein aquarius
+Macromolecule #13: SNW domain-containing protein 1
+Macromolecule #14: Peptidyl-prolyl cis-trans isomerase-like 1
+Macromolecule #15: Pre-mRNA-processing factor 17
+Macromolecule #16: Coiled-coil domain-containing protein 12
+Macromolecule #17: Small nuclear ribonucleoprotein Sm D3
+Macromolecule #18: Small nuclear ribonucleoprotein Sm D1
+Macromolecule #19: Small nuclear ribonucleoprotein Sm D2
+Macromolecule #20: Small nuclear ribonucleoprotein E
+Macromolecule #21: Small nuclear ribonucleoprotein F
+Macromolecule #22: Small nuclear ribonucleoprotein G
+Macromolecule #23: Pre-mRNA-processing factor 19
+Macromolecule #24: Splicing regulator SDE2
+Macromolecule #25: Splicing factor ESS-2 homolog
+Macromolecule #27: Pre-mRNA-processing-splicing factor 8
+Macromolecule #28: Pre-mRNA-splicing factor SYF1
+Macromolecule #30: Cell division cycle 5-like protein
+Macromolecule #31: CWF19-like protein 2
+Macromolecule #32: Pre-mRNA-splicing factor SYF2
+Macromolecule #33: Spliceosome-associated protein CWC15 homolog
+Macromolecule #34: PAX3- and PAX7-binding protein 1
+Macromolecule #35: Pleiotropic regulator 1
+Macromolecule #36: Tuftelin-interacting protein 11
+Macromolecule #37: Small nuclear ribonucleoprotein-associated proteins B and B'
+Macromolecule #38: GUANOSINE-5'-TRIPHOSPHATE
+Macromolecule #39: ZINC ION
+Macromolecule #40: INOSITOL HEXAKISPHOSPHATE
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.9 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.75 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 87951 |
Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |