CTNNBL1 facilitates the association of CWC15 with CDC5L and is required to maintain the abundance of the Prp19 spliceosomal complex

Nucleic Acids Res. 2015 Aug 18;43(14):7058-69. doi: 10.1093/nar/gkv643. Epub 2015 Jun 29.


In order to catalyse the splicing of messenger RNA, multiple proteins and RNA components associate and dissociate in a dynamic highly choreographed process. The Prp19 complex is a conserved essential part of the splicing machinery thought to facilitate the conformational changes the spliceosome undergoes during catalysis. Dynamic protein interactions often involve highly disordered regions that are difficult to study by structural methods. Using amine crosslinking and hydrogen-deuterium exchange coupled to mass spectrometry, we describe the architecture of the Prp19 sub-complex that contains CTNNBL1. Deficiency in CTNNBL1 leads to delayed initiation of cell division and embryonic lethality. Here we show that in vitro CTNNBL1 enhances the association of CWC15 and CDC5L, both core Prp19 complex proteins and identify an overlap in the region of CDC5L that binds either CTNNBL1 or CWC15 suggesting the two proteins might exchange places in the complex. Furthermore, in vivo, CTNNBL1 is required to maintain normal levels of the Prp19 complex and to facilitate the interaction of CWC15 with CDC5L. Our results identify a chaperone function for CTNNBL1 within the essential Prp19 complex, a function required to maintain the integrity of the complex and to support efficient splicing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / chemistry
  • Apoptosis Regulatory Proteins / metabolism*
  • Apoptosis Regulatory Proteins / physiology
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • HEK293 Cells
  • Humans
  • Mice
  • Models, Molecular
  • Nuclear Matrix-Associated Proteins / metabolism*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Nuclear Proteins / physiology
  • RNA Splicing Factors
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism*
  • Spliceosomes / metabolism


  • Apoptosis Regulatory Proteins
  • CDC5L protein, human
  • CTNNBL1 protein, human
  • CWC15 protein, human
  • Cell Cycle Proteins
  • Nuclear Matrix-Associated Proteins
  • Nuclear Proteins
  • Prpf19 protein, mouse
  • RNA Splicing Factors
  • RNA-Binding Proteins