CWC22 connects pre-mRNA splicing and exon junction complex assembly

Cell Rep. 2012 Sep 27;2(3):454-61. doi: 10.1016/j.celrep.2012.08.017. Epub 2012 Sep 6.


The exon junction complex (EJC) is a key regulator of posttranscriptional mRNA fate and binds to mRNA during splicing. Although the composition of EJCs is well understood, the mechanism mediating splicing-dependent EJC assembly and the factor(s) recruiting the EJC remain elusive. Here, we identify CWC22 as an essential splicing factor that is required for EJC assembly. In CWC22-depleted cells, pre-mRNA splicing is impaired but is rescued by a central fragment of CWC22. We show that the MIF4G domain of CWC22 initiates EJC assembly via a direct interaction with the EJC core protein eIF4A3, and we characterize mutations in eIF4A3 that abolish binding to CWC22. These eIF4A3 mutants efficiently nucleate splicing-independent recombinant EJC core complexes, but they fail to support splicing-dependent EJC deposition. Our work establishes a direct link between the splicing machinery and the EJC, hence uncovering a molecular interaction at the center of a posttranscriptional gene regulation network.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • Eukaryotic Initiation Factor-4A / genetics
  • Eukaryotic Initiation Factor-4A / metabolism
  • Gene Expression Regulation / physiology
  • HeLa Cells
  • Humans
  • Nuclear Proteins
  • Peptidylprolyl Isomerase
  • RNA Precursors / genetics
  • RNA Precursors / metabolism*
  • RNA Splicing / physiology*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*


  • CWC22 protein, human
  • Carrier Proteins
  • Nuclear Proteins
  • RNA Precursors
  • RNA-Binding Proteins
  • Eukaryotic Initiation Factor-4A
  • EIF4A3 protein, human
  • DEAD-box RNA Helicases
  • Peptidylprolyl Isomerase