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Yorodumi- EMDB-19399: Integrative Structure of the human intron lariat Spliceosome (ILS'') -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-19399 | |||||||||
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Title | Integrative Structure of the human intron lariat Spliceosome (ILS'') | |||||||||
Map data | composite map | |||||||||
Sample |
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Keywords | mRNA / splicing / intron lariat spliceosome / pre-mRNA | |||||||||
Function / homology | Function and homology information RNA lariat debranching enzyme activator activity / : / post-spliceosomal complex / negative regulation of double-strand break repair via nonhomologous end joining / U2-type post-mRNA release spliceosomal complex / biomineral tissue development / spliceosomal complex disassembly / protection from non-homologous end joining at telomere / regulation of skeletal muscle satellite cell proliferation / positive regulation of myoblast proliferation ...RNA lariat debranching enzyme activator activity / : / post-spliceosomal complex / negative regulation of double-strand break repair via nonhomologous end joining / U2-type post-mRNA release spliceosomal complex / biomineral tissue development / spliceosomal complex disassembly / protection from non-homologous end joining at telomere / regulation of skeletal muscle satellite cell proliferation / positive regulation of myoblast proliferation / regulation of retinoic acid receptor signaling pathway / post-mRNA release spliceosomal complex / U2 snRNP binding / endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / U7 snRNA binding / histone pre-mRNA DCP binding / 3'-5' RNA helicase activity / U7 snRNP / generation of catalytic spliceosome for first transesterification step / histone methyltransferase binding / regulation of vitamin D receptor signaling pathway / histone pre-mRNA 3'end processing complex / SLBP independent Processing of Histone Pre-mRNAs / SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs / protein methylation / U12-type spliceosomal complex / embryonic brain development / methylosome / nuclear retinoic acid receptor binding / 7-methylguanosine cap hypermethylation / positive regulation of androgen receptor activity / Prp19 complex / U1 snRNP binding / pICln-Sm protein complex / mRNA 3'-end processing / ATP-dependent activity, acting on RNA / sno(s)RNA-containing ribonucleoprotein complex / snRNP binding / U2-type catalytic step 1 spliceosome / RNA splicing, via transesterification reactions / small nuclear ribonucleoprotein complex / pre-mRNA binding / SMN-Sm protein complex / response to alkaloid / telomerase RNA binding / spliceosomal tri-snRNP complex / telomerase holoenzyme complex / P granule / U2-type spliceosomal complex / U2-type precatalytic spliceosome / positive regulation by host of viral transcription / mRNA cis splicing, via spliceosome / positive regulation of vitamin D receptor signaling pathway / commitment complex / U2-type prespliceosome assembly / nuclear vitamin D receptor binding / Transport of Mature mRNA derived from an Intron-Containing Transcript / U2-type catalytic step 2 spliceosome / Notch binding / Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells / U4 snRNP / positive regulation of mRNA splicing, via spliceosome / RUNX3 regulates NOTCH signaling / U2 snRNP / NOTCH4 Intracellular Domain Regulates Transcription / RNA Polymerase II Transcription Termination / U1 snRNP / ubiquitin-ubiquitin ligase activity / NOTCH3 Intracellular Domain Regulates Transcription / WD40-repeat domain binding / positive regulation of neurogenesis / U2-type prespliceosome / lipid biosynthetic process / nuclear androgen receptor binding / snoRNA binding / precatalytic spliceosome / K63-linked polyubiquitin modification-dependent protein binding / muscle organ development / cyclosporin A binding / Notch-HLH transcription pathway / generation of catalytic spliceosome for second transesterification step / positive regulation of transforming growth factor beta receptor signaling pathway / Formation of paraxial mesoderm / mRNA Splicing - Minor Pathway / spliceosomal complex assembly / SMAD binding / mitotic G2 DNA damage checkpoint signaling / protein K63-linked ubiquitination / mRNA 3'-splice site recognition / protein peptidyl-prolyl isomerization / blastocyst development / protein localization to nucleus / spliceosomal tri-snRNP complex assembly / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / embryonic organ development / transcription-coupled nucleotide-excision repair / U5 snRNA binding / U5 snRNP / negative regulation of protein-containing complex assembly / positive regulation of G1/S transition of mitotic cell cycle Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Rothe P / Vorlaender MK / Plaschka C | |||||||||
Funding support | European Union, 1 items
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Citation | Journal: Nature / Year: 2024 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 | emd_19399.map.gz | 8 MB | EMDB map data format | |
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Header (meta data) | emd-19399-v30.xml emd-19399.xml | 61.3 KB 61.3 KB | Display Display | EMDB header |
Images | emd_19399.png | 96.2 KB | ||
Filedesc metadata | emd-19399.cif.gz | 18.7 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-19399 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-19399 | HTTPS FTP |
-Validation report
Summary document | emd_19399_validation.pdf.gz | 374.7 KB | Display | EMDB validaton report |
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Full document | emd_19399_full_validation.pdf.gz | 374.3 KB | Display | |
Data in XML | emd_19399_validation.xml.gz | 7.1 KB | Display | |
Data in CIF | emd_19399_validation.cif.gz | 8.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-19399 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-19399 | HTTPS FTP |
-Related structure data
Related structure data | 8ro2MC 8ro0C 8ro1C 9fmdC 50477 50478 50479 50480 50481 50482 50483 50484 50485 50486 50487 50488 50489 50490 M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_19399.map.gz / Format: CCP4 / Size: 282.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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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
-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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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.9 |
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Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN |
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 |
-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 |