6V4X

Cryo-EM structure of an active human histone pre-mRNA 3'-end processing machinery at 3.2 Angstrom resolution


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.20 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structure of an active human histone pre-mRNA 3'-end processing machinery.

Sun, Y.Zhang, Y.Aik, W.S.Yang, X.C.Marzluff, W.F.Walz, T.Dominski, Z.Tong, L.

(2020) Science 367: 700-703

  • DOI: https://doi.org/10.1126/science.aaz7758
  • Primary Citation of Related Structures:  
    6V4X

  • PubMed Abstract: 

    The 3'-end processing machinery for metazoan replication-dependent histone precursor messenger RNAs (pre-mRNAs) contains the U7 small nuclear ribonucleoprotein and shares the key cleavage module with the canonical cleavage and polyadenylation machinery. We reconstituted an active human histone pre-mRNA processing machinery using 13 recombinant proteins and two RNAs and determined its structure by cryo-electron microscopy. The overall structure is highly asymmetrical and resembles an amphora with one long handle. We captured the pre-mRNA in the active site of the endonuclease, the 73-kilodalton subunit of the cleavage and polyadenylation specificity factor, poised for cleavage. The endonuclease and the entire cleavage module undergo extensive rearrangements for activation, triggered through the recognition of the duplex between the authentic pre-mRNA and U7 small nuclear RNA (snRNA). Our study also has notable implications for understanding canonical and snRNA 3'-end processing.


  • Organizational Affiliation

    Department of Biological Sciences, Columbia University, New York, NY 10027, USA.


Macromolecules

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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Small nuclear ribonucleoprotein Sm D3146Homo sapiensMutation(s): 0 
Gene Names: SNRPD3
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Find proteins for P62318 (Homo sapiens)
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PHAROS:  P62318
GTEx:  ENSG00000100028 
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UniProt GroupP62318
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Small nuclear ribonucleoprotein-associated proteins B and B'95Homo sapiensMutation(s): 0 
Gene Names: SNRPBCODSNRPB1
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Find proteins for P14678 (Homo sapiens)
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PHAROS:  P14678
GTEx:  ENSG00000125835 
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UniProt GroupP14678
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Small nuclear ribonucleoprotein FC [auth F]86Homo sapiensMutation(s): 0 
Gene Names: SNRPFPBSCF
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Find proteins for P62306 (Homo sapiens)
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PHAROS:  P62306
GTEx:  ENSG00000139343 
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UniProt GroupP62306
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Small nuclear ribonucleoprotein ED [auth E]92Homo sapiensMutation(s): 0 
Gene Names: SNRPE
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Find proteins for P62304 (Homo sapiens)
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PHAROS:  P62304
GTEx:  ENSG00000182004 
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UniProt GroupP62304
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
Small nuclear ribonucleoprotein GE [auth G]84Homo sapiensMutation(s): 0 
Gene Names: SNRPGPBSCG
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Find proteins for P62308 (Homo sapiens)
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GTEx:  ENSG00000143977 
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UniProt GroupP62308
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Entity ID: 6
MoleculeChains Sequence LengthOrganismDetailsImage
U7 snRNA-associated Sm-like protein LSm10F [auth C]123Homo sapiensMutation(s): 0 
Gene Names: LSM10
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Find proteins for Q969L4 (Homo sapiens)
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PHAROS:  Q969L4
GTEx:  ENSG00000181817 
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UniProt GroupQ969L4
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Entity ID: 7
MoleculeChains Sequence LengthOrganismDetailsImage
U7 snRNA-associated Sm-like protein LSm11G [auth D]259Homo sapiensMutation(s): 0 
Gene Names: LSM11
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PHAROS:  P83369
GTEx:  ENSG00000155858 
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UniProt GroupP83369
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Entity ID: 8
MoleculeChains Sequence LengthOrganismDetailsImage
Cleavage and polyadenylation specificity factor subunit 3684Homo sapiensMutation(s): 0 
Gene Names: CPSF3CPSF73
EC: 3.1.27
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Find proteins for Q9UKF6 (Homo sapiens)
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PHAROS:  Q9UKF6
GTEx:  ENSG00000119203 
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UniProt GroupQ9UKF6
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Entity ID: 9
MoleculeChains Sequence LengthOrganismDetailsImage
Cleavage and polyadenylation specificity factor subunit 2782Homo sapiensMutation(s): 0 
Gene Names: CPSF2CPSF100KIAA1367
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GTEx:  ENSG00000165934 
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UniProt GroupQ9P2I0
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Entity ID: 10
MoleculeChains Sequence LengthOrganismDetailsImage
Symplekin1,072Homo sapiensMutation(s): 0 
Gene Names: SYMPKSPK
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Find proteins for Q92797 (Homo sapiens)
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PHAROS:  Q92797
GTEx:  ENSG00000125755 
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UniProt GroupQ92797
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Entity ID: 11
MoleculeChains LengthOrganismImage
U7 snRNAK [auth Z]60Homo sapiens
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Entity ID: 12
MoleculeChains LengthOrganismImage
modified H2a pre-mRNAL [auth Y]52Mus musculus
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Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.20 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
RECONSTRUCTIONRELION

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR35GM118093
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR01GM029832

Revision History  (Full details and data files)

  • Version 1.0: 2020-02-19
    Type: Initial release
  • Version 1.1: 2022-03-16
    Changes: Author supporting evidence, Database references, Derived calculations
  • Version 1.2: 2024-05-29
    Changes: Data collection