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Yorodumi- EMDB-50484: Integrative Structure of the human intron lariat Spliceosome (ILS... -
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Basic information
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| Title | Integrative Structure of the human intron lariat Spliceosome (ILS'') (Map 8) | |||||||||
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Keywords | mRNA / splicing / intron lariat spliceosome / pre-mRNA | |||||||||
| Biological species | Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.24 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_50484.map.gz | 142.5 MB | EMDB map data format | |
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| Header (meta data) | emd-50484-v30.xml emd-50484.xml | 20.4 KB 20.4 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_50484_fsc.xml | 13.8 KB | Display | FSC data file |
| Images | emd_50484.png | 137.5 KB | ||
| Filedesc metadata | emd-50484.cif.gz | 4.2 KB | ||
| Others | emd_50484_additional_1.map.gz emd_50484_half_map_1.map.gz emd_50484_half_map_2.map.gz | 266.7 MB 262.5 MB 262.5 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-50484 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-50484 | HTTPS FTP |
-Validation report
| Summary document | emd_50484_validation.pdf.gz | 1.1 MB | Display | EMDB validaton report |
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| Full document | emd_50484_full_validation.pdf.gz | 1.1 MB | Display | |
| Data in XML | emd_50484_validation.xml.gz | 22.5 KB | Display | |
| Data in CIF | emd_50484_validation.cif.gz | 29.6 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-50484 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-50484 | HTTPS FTP |
-Related structure data
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Map
| File | Download / File: emd_50484.map.gz / Format: CCP4 / Size: 282.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 1.2375 Å | ||||||||||||||||||||||||||||||||||||
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Additional map: #1
| File | emd_50484_additional_1.map | ||||||||||||
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-Half map: #1
| File | emd_50484_half_map_1.map | ||||||||||||
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-Half map: #2
| File | emd_50484_half_map_2.map | ||||||||||||
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Sample components
-Entire : human intron lariat spliceosome
| Entire | Name: human intron lariat spliceosome |
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| Components |
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-Supramolecule #1: human intron lariat spliceosome
| Supramolecule | Name: human intron lariat spliceosome / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1, #3-#14, #36, #15-#35, #2 Details: endogenous complex purified from K562 nuclear extract using a TFIP11-GFP tagged over-expression lent viral cell line. |
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| Source (natural) | Organism: Homo sapiens (human) |
-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: 7.4 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Image recording | Film or detector model: TFS FALCON 4i (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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Keywords
Homo sapiens (human)
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Processing
FIELD EMISSION GUN

