Dynamic protein-protein interaction wiring of the human spliceosome

Mol Cell. 2012 Feb 24;45(4):567-80. doi: 10.1016/j.molcel.2011.12.034.


More than 200 proteins copurify with spliceosomes, the compositionally dynamic RNPs catalyzing pre-mRNA splicing. To better understand protein - protein interactions governing splicing, we systematically investigated interactions between human spliceosomal proteins. A comprehensive Y2H interaction matrix screen generated a protein interaction map comprising 632 interactions between 196 proteins. Among these, 242 interactions were found between spliceosomal core proteins and largely validated by coimmunoprecipitation. To reveal dynamic changes in protein interactions, we integrated spliceosomal complex purification information with our interaction data and performed link clustering. These data, together with interaction competition experiments, suggest that during step 1 of splicing, hPRP8 interactions with SF3b proteins are replaced by hSLU7, positioning this second step factor close to the active site, and that the DEAH-box helicases hPRP2 and hPRP16 cooperate through ordered interactions with GPKOW. Our data provide extensive information about the spliceosomal protein interaction network and its dynamics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding, Competitive
  • Carrier Proteins / metabolism
  • Cluster Analysis
  • DEAD-box RNA Helicases / metabolism
  • DEAD-box RNA Helicases / physiology
  • Humans
  • Protein Interaction Domains and Motifs*
  • Protein Interaction Maps
  • Proteomics
  • RNA Helicases / metabolism
  • RNA Helicases / physiology
  • RNA Precursors / metabolism*
  • RNA Splicing Factors
  • RNA Splicing*
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / metabolism
  • RNA-Binding Proteins / physiology
  • Ribonucleoproteins, Small Nuclear / metabolism
  • Spliceosomes / metabolism*


  • Carrier Proteins
  • PRPF8 protein, human
  • RNA Precursors
  • RNA Splicing Factors
  • RNA, Messenger
  • RNA-Binding Proteins
  • Ribonucleoproteins, Small Nuclear
  • SLU7 protein, human
  • DHX16 protein, human
  • DHX38 protein, human
  • DEAD-box RNA Helicases
  • RNA Helicases