Structures of the human pre-catalytic spliceosome and its precursor spliceosome

Cell Res. 2018 Dec;28(12):1129-1140. doi: 10.1038/s41422-018-0094-7. Epub 2018 Oct 12.


The pre-catalytic spliceosome (B complex) is preceded by its precursor spliceosome (pre-B complex) and followed by the activated spliceosome (Bact complex). The pre-B-to-B and B-to-Bact 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cryoelectron Microscopy / methods*
  • DEAD-box RNA Helicases / chemistry*
  • Humans
  • Models, Molecular
  • RNA Splicing
  • RNA Splicing Factors / chemistry*
  • Ribonucleoproteins, Small Nuclear / chemistry*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Spliceosomes / chemistry*


  • RNA Splicing Factors
  • Ribonucleoproteins, Small Nuclear
  • Saccharomyces cerevisiae Proteins
  • DDX23 protein, human
  • PRP28 protein, S cerevisiae
  • DEAD-box RNA Helicases