Structure of a human catalytic step I spliceosome

Science. 2018 Feb 2;359(6375):537-545. doi: 10.1126/science.aar6401. Epub 2018 Jan 4.


Splicing by the spliceosome involves branching and exon ligation. The branching reaction leads to the formation of the catalytic step I spliceosome (C complex). Here we report the cryo-electron microscopy structure of the human C complex at an average resolution of 4.1 angstroms. Compared with the Saccharomyces cerevisiae C complex, the human complex contains 11 additional proteins. The step I splicing factors CCDC49 and CCDC94 (Cwc25 and Yju2 in S. cerevisiae, respectively) closely interact with the DEAH-family adenosine triphosphatase/helicase Prp16 and bridge the gap between Prp16 and the active-site RNA elements. These features, together with structural comparison of the human C and C* complexes, provide mechanistic insights into ribonucleoprotein remodeling and allow the proposition of a working mechanism for the C-to-C* transition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Biocatalysis
  • Catalytic Domain
  • Cryoelectron Microscopy
  • DEAD-box RNA Helicases / chemistry*
  • DEAD-box RNA Helicases / ultrastructure
  • Humans
  • Models, Molecular
  • RNA Splicing Factors / chemistry*
  • RNA Splicing Factors / ultrastructure
  • RNA Splicing*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / ultrastructure
  • Spliceosomes / chemistry*
  • Spliceosomes / ultrastructure


  • RNA Splicing Factors
  • Saccharomyces cerevisiae Proteins
  • DEAD-box RNA Helicases