Evolution of the Early Spliceosomal Complex-From Constitutive to Regulated Splicing

Int J Mol Sci. 2021 Nov 18;22(22):12444. doi: 10.3390/ijms222212444.


Pre-mRNA splicing is a major process in the regulated expression of genes in eukaryotes, and alternative splicing is used to generate different proteins from the same coding gene. Splicing is a catalytic process that removes introns and ligates exons to create the RNA sequence that codifies the final protein. While this is achieved in an autocatalytic process in ancestral group II introns in prokaryotes, the spliceosome has evolved during eukaryogenesis to assist in this process and to finally provide the opportunity for intron-specific splicing. In the early stage of splicing, the RNA 5' and 3' splice sites must be brought within proximity to correctly assemble the active spliceosome and perform the excision and ligation reactions. The assembly of this first complex, termed E-complex, is currently the least understood process. We focused in this review on the formation of the E-complex and compared its composition and function in three different organisms. We highlight the common ancestral mechanisms in S. cerevisiae, S. pombe, and mammals and conclude with a unifying model for intron definition in constitutive and regulated co-transcriptional splicing.

Keywords: 5′ splicing site; E-complex; Prp2; U2AF65; exon–intron junction; fission yeast; spliceosome; splicing.

Publication types

  • Review

MeSH terms

  • Alternative Splicing*
  • Animals
  • Base Sequence
  • Evolution, Molecular
  • Exons
  • Humans
  • Introns
  • Mammals / genetics*
  • Mammals / metabolism
  • RNA Precursors / genetics*
  • RNA Precursors / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Ribonucleoprotein, U1 Small Nuclear / genetics
  • Ribonucleoprotein, U1 Small Nuclear / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces / metabolism
  • Spliceosomes / chemistry
  • Spliceosomes / genetics*
  • Spliceosomes / metabolism
  • Splicing Factor U2AF / genetics
  • Splicing Factor U2AF / metabolism


  • Prp40 protein, S cerevisiae
  • RNA Precursors
  • RNA, Messenger
  • Ribonucleoprotein, U1 Small Nuclear
  • Saccharomyces cerevisiae Proteins
  • Splicing Factor U2AF
  • U2AF2 protein, human