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Structure paper

TitleStructures of the human pre-catalytic spliceosome and its precursor spliceosome.
Journal, issue, pagesCell Res, Vol. 28, Issue 12, Page 1129-1140, Year 2018
Publish dateOct 12, 2018
AuthorsXiechao Zhan / Chuangye Yan / Xiaofeng Zhang / Jianlin Lei / Yigong Shi /
PubMed AbstractThe pre-catalytic spliceosome (B complex) is preceded by its precursor spliceosome (pre-B complex) and followed by the activated spliceosome (B complex). The pre-B-to-B and B-to-B transitions are ...The pre-catalytic spliceosome (B complex) is preceded by its precursor spliceosome (pre-B complex) and followed by the activated spliceosome (B complex). The pre-B-to-B and B-to-B transitions are driven by the ATPase/helicases Prp28 and Brr2, respectively. In this study, we report the cryo-electron microscopy structures of the human pre-B complex and the human B complex at an average resolution of 5.7 and 3.8 Å, respectively. In the pre-B complex, U1 and U2 small nuclear ribonucleoproteins (snRNPs) associate with two edges of the tetrahedron-shaped U4/U6.U5 tri-snRNP. The pre-mRNA is yet to be recognized by U5 or U6 small nuclear RNA (snRNA), and loop I of U5 snRNA remains unengaged. In the B complex, U1 snRNP and Prp28 are dissociated, the 5'-exon is anchored to loop I of U5 snRNA, and the 5'-splice site is recognized by U6 snRNA through duplex formation. In sharp contrast to S. cerevisiae, most components of U2 snRNP and tri-snRNP, exemplified by Brr2, undergo pronounced rearrangements in the human pre-B-to-B transition. Structural analysis reveals mechanistic insights into the assembly and activation of the human spliceosome.
External linksCell Res / PubMed:30315277 / PubMed Central
MethodsEM (single particle)
Resolution3.8 - 5.7 Å
Structure data

9621

6ah0

EMDB-9621, PDB-6ah0:
The Cryo-EM Structure of the Precusor of Human Pre-catalytic Spliceosome (pre-B complex)
Method: EM (single particle) / Resolution: 5.7 Å

9624

6ahd

EMDB-9624, PDB-6ahd:
The Cryo-EM Structure of Human Pre-catalytic Spliceosome (B complex) at 3.8 angstrom resolution
Method: EM (single particle) / Resolution: 3.8 Å

Chemicals

ChemComp-IHP:
INOSITOL HEXAKISPHOSPHATE

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

Source
  • homo sapiens (human)
KeywordsSPLICING / Spliceosome

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