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Yorodumi- PDB-8ro2: Integrative Structure of the human intron lariat Spliceosome (ILS'') -
+Open data
-Basic information
Entry | Database: PDB / ID: 8ro2 | ||||||
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Title | Integrative Structure of the human intron lariat Spliceosome (ILS'') | ||||||
Components |
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Keywords | SPLICING / mRNA / 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 / post-mRNA release spliceosomal complex / regulation of retinoic acid receptor signaling pathway / 3'-5' RNA helicase activity / U2 snRNP binding / endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / U7 snRNA binding / histone pre-mRNA DCP binding / 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 / embryonic brain development / U12-type spliceosomal complex / methylosome / nuclear retinoic acid receptor binding / 7-methylguanosine cap hypermethylation / positive regulation of androgen receptor activity / Prp19 complex / U1 snRNP binding / snRNP binding / mRNA 3'-end processing / ATP-dependent activity, acting on RNA / pICln-Sm protein complex / RNA splicing, via transesterification reactions / U2-type catalytic step 1 spliceosome / small nuclear ribonucleoprotein complex / pre-mRNA binding / sno(s)RNA-containing ribonucleoprotein complex / SMN-Sm protein complex / response to alkaloid / telomerase RNA binding / spliceosomal tri-snRNP complex / telomerase holoenzyme complex / P granule / positive regulation by host of viral transcription / U2-type precatalytic spliceosome / U2-type spliceosomal complex / mRNA cis splicing, via spliceosome / positive regulation of vitamin D receptor signaling pathway / commitment complex / Transport of Mature mRNA derived from an Intron-Containing Transcript / U2-type prespliceosome assembly / nuclear vitamin D receptor binding / 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 / muscle organ development / U1 snRNP / positive regulation of neurogenesis / ubiquitin-ubiquitin ligase activity / NOTCH3 Intracellular Domain Regulates Transcription / lipid biosynthetic process / WD40-repeat domain binding / U2-type prespliceosome / nuclear androgen receptor binding / snoRNA binding / precatalytic spliceosome / K63-linked polyubiquitin modification-dependent protein binding / 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 / blastocyst development / protein peptidyl-prolyl isomerization / protein localization to nucleus / spliceosomal tri-snRNP complex assembly / transcription-coupled nucleotide-excision repair / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / retinoic acid receptor signaling pathway / U5 snRNA binding / U5 snRNP / positive regulation of G1/S transition of mitotic cell cycle / proteasomal protein catabolic process Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||
Authors | Rothe, P. / Vorlaender, M.K. / Plaschka, C. | ||||||
Funding support | European Union, 1items
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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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ro2.cif.gz | 2.1 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8ro2.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8ro2.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8ro2_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 8ro2_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 8ro2_validation.xml.gz | 247 KB | Display | |
Data in CIF | 8ro2_validation.cif.gz | 423.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ro/8ro2 ftp://data.pdbj.org/pub/pdb/validation_reports/ro/8ro2 | HTTPS FTP |
-Related structure data
Related structure data | 19399MC 8ro0C 8ro1C 9fmdC 50477 50478 50479 50480 50481 50482 50483 50484 50485 50486 50487 50488 50489 50490 C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-RNA chain , 4 types, 4 molecules 265IN
#1: RNA chain | Mass: 60186.445 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 36516 |
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#2: RNA chain | Mass: 34098.270 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: NR_004394.1 |
#26: RNA chain | Mass: 36908.668 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 36515 |
#29: RNA chain | Mass: 30153.607 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
-Protein , 18 types, 18 molecules CDXEJNQRSZz3ALPPXTTFb
#3: Protein | Mass: 109560.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q15029 |
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#5: Protein | Mass: 91065.805 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O43143, RNA helicase |
#6: Protein | Mass: 39359.492 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q96DI7 |
#7: Protein | Mass: 100610.008 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9BZJ0 |
#10: Protein | Mass: 17032.850 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P41223 |
#12: Protein | Mass: 171502.453 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O60306, RNA helicase |
#13: Protein | Mass: 61770.648 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q13573 |
#14: Protein | Mass: 18257.805 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9Y3C6, peptidylprolyl isomerase |
#16: Protein | Mass: 19223.850 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q8WUD4 |
#24: Protein | Mass: 49818.027 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q6IQ49 |
#25: Protein | Mass: 52639.953 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q96DF8 |
#27: Protein | Mass: 273974.250 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q6P2Q9 |
#30: Protein | Mass: 92406.883 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q99459 |
#33: Protein | Mass: 26674.447 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9P013 |
#34: Protein | Mass: 104953.656 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9Y5B6 |
#35: Protein | Mass: 57280.758 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O43660 |
#36: Protein | Mass: 96945.727 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9UBB9 |
#37: Protein | Mass: 24642.131 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P14678 |
-Pre-mRNA-splicing factor ... , 5 types, 5 molecules DKOIM
#4: Protein | Mass: 33046.254 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9ULR0 |
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#8: Protein | Mass: 26163.420 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O75934 |
#11: Protein | Mass: 46959.555 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9NW64 |
#28: Protein | Mass: 100148.711 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9HCS7 |
#32: Protein | Mass: 28780.518 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O95926 |
-CWF19-like protein ... , 2 types, 2 molecules L1L2
#9: Protein | Mass: 60696.922 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q69YN2 |
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#31: Protein | Mass: 103976.492 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q2TBE0 |
-Pre-mRNA-processing factor ... , 2 types, 5 molecules Wsqrt
#15: Protein | Mass: 65612.180 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O60508 |
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#23: Protein | Mass: 55245.547 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: Q9UMS4, RING-type E3 ubiquitin transferase |
-Small nuclear ribonucleoprotein ... , 6 types, 6 molecules acdefg
#17: Protein | Mass: 13940.308 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62318 |
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#18: Protein | Mass: 13310.653 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62314 |
#19: Protein | Mass: 13551.928 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62316 |
#20: Protein | Mass: 10817.601 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62304 |
#21: Protein | Mass: 9734.171 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62306 |
#22: Protein | Mass: 8508.084 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62308 |
-Non-polymers , 3 types, 5 molecules
#38: Chemical | ChemComp-GTP / | ||
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#39: Chemical | #40: Chemical | ChemComp-IHP / | |
-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Human Intron-lariat splicoesome / Type: COMPLEX Entity ID: #1, #25-#26, #2, #27, #3-#6, #28-#29, #7-#8, #30, #9, #31-#32, #10-#11, #33-#34, #12-#14, #35-#36, #15-#17, #37, #18-#24 Source: NATURAL |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.9 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 750 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 87951 / Symmetry type: POINT |