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Yorodumi- 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'') | |||||||||
Map data | composite map | |||||||||
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Keywords | mRNA / splicing / intron lariat spliceosome / pre-mRNA | |||||||||
| Function / homology | Function and homology informationRNA lariat debranching enzyme activator activity / U2-type post-mRNA release spliceosomal complex / spliceosomal complex disassembly / negative regulation of double-strand break repair via nonhomologous end joining / regulation of vitamin D receptor signaling pathway / biomineral tissue development / protection from non-homologous end joining at telomere / regulation of retinoic acid receptor signaling pathway / U2 snRNP binding / U7 snRNA binding ...RNA lariat debranching enzyme activator activity / U2-type post-mRNA release spliceosomal complex / spliceosomal complex disassembly / negative regulation of double-strand break repair via nonhomologous end joining / regulation of vitamin D receptor signaling pathway / biomineral tissue development / protection from non-homologous end joining at telomere / regulation of retinoic acid receptor signaling pathway / U2 snRNP binding / U7 snRNA binding / histone pre-mRNA DCP binding / U7 snRNP / generation of catalytic spliceosome for first transesterification step / 3'-5' RNA helicase activity / histone methyltransferase binding / histone pre-mRNA 3'end processing complex / nuclear histone mRNA catabolic process / endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / U4atac snRNP / SLBP independent Processing of Histone Pre-mRNAs / SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs / U4atac/U6atac snRNP / U11/U12 snRNP / U4atac/U6atac x U5 tri-snRNP complex / embryonic brain development / 7-methylguanosine cap hypermethylation / response to alkaloid / U12-type spliceosomal complex / muscle organ development / U1 snRNP binding / nuclear retinoic acid receptor binding / post-spliceosomal complex / positive regulation of mRNA splicing, via spliceosome / RNA splicing, via transesterification reactions / pICln-Sm protein complex / snRNP binding / ATP-dependent activity, acting on RNA / mRNA 3'-end processing / sno(s)RNA-containing ribonucleoprotein complex / methylosome / U12-type catalytic step 2 spliceosome / small nuclear ribonucleoprotein complex / RNA Polymerase II Transcription Termination / SMN-Sm protein complex / post-mRNA release spliceosomal complex / U12-type precatalytic spliceosome / spliceosomal tri-snRNP complex / positive regulation of vitamin D receptor signaling pathway / P granule / commitment complex / host-mediated activation of viral transcription / U2-type precatalytic spliceosome / Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells / RUNX3 regulates NOTCH signaling / Notch binding / U2-type spliceosomal complex / nuclear vitamin D receptor binding / telomerase holoenzyme complex / Transport of Mature mRNA derived from an Intron-Containing Transcript / U2-type prespliceosome assembly / NOTCH4 Intracellular Domain Regulates Transcription / telomerase RNA binding / pre-mRNA binding / positive regulation of neurogenesis / U4/U6 snRNP / U2-type catalytic step 2 spliceosome / spliceosome conformational change to release U4 (or U4atac) and U1 (or U11) / U1 snRNP / U2 snRNP / NOTCH3 Intracellular Domain Regulates Transcription / protein methylation / U2-type catalytic step 1 spliceosome / U4 snRNP / mRNA stabilization / U2-type prespliceosome / mRNA cis splicing, via spliceosome / protein peptidyl-prolyl isomerization / nuclear androgen receptor binding / K63-linked polyubiquitin modification-dependent protein binding / generation of catalytic spliceosome for second transesterification step / snoRNA binding / ubiquitin-ubiquitin ligase activity / Notch-HLH transcription pathway / Formation of paraxial mesoderm / precatalytic spliceosome / positive regulation of transforming growth factor beta receptor signaling pathway / WD40-repeat domain binding / mRNA 3'-splice site recognition / SMAD binding / mRNA Splicing - Minor Pathway / spliceosomal complex assembly / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / Prp19 complex / negative regulation of mRNA splicing, via spliceosome / U5 snRNA binding / spliceosomal tri-snRNP complex assembly / U5 snRNP / U6 snRNA binding / U4/U6 x U5 tri-snRNP complex / Cajal body 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: 2024Title: 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. | |||||||||
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Structure visualization
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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 | https://data.pdbj.org/pub/emdb/structures/EMD-19399 ftp://data.pdbj.org/pub/emdb/structures/EMD-19399 | 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 F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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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
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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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Processing | 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: 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 |
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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 |
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Keywords
Homo sapiens (human)
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FIELD EMISSION GUN

