SNEV is an evolutionarily conserved splicing factor whose oligomerization is necessary for spliceosome assembly

Nucleic Acids Res. 2005 Dec 6;33(21):6868-83. doi: 10.1093/nar/gki986. Print 2005.


We have isolated the human protein SNEV as downregulated in replicatively senescent cells. Sequence homology to the yeast splicing factor Prp19 suggested that SNEV might be the orthologue of Prp19 and therefore might also be involved in pre-mRNA splicing. We have used various approaches including gene complementation studies in yeast using a temperature sensitive mutant with a pleiotropic phenotype and SNEV immunodepletion from human HeLa nuclear extracts to determine its function. A human-yeast chimera was indeed capable of restoring the wild-type phenotype of the yeast mutant strain. In addition, immunodepletion of SNEV from human nuclear extracts resulted in a decrease of in vitro pre-mRNA splicing efficiency. Furthermore, as part of our analysis of protein-protein interactions within the CDC5L complex, we found that SNEV interacts with itself. The self-interaction domain was mapped to amino acids 56-74 in the protein's sequence and synthetic peptides derived from this region inhibit in vitro splicing by surprisingly interfering with spliceosome formation and stability. These results indicate that SNEV is the human orthologue of yeast PRP19, functions in splicing and that homo-oligomerization of SNEV in HeLa nuclear extract is essential for spliceosome assembly and that it might also be important for spliceosome stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Nucleus / chemistry
  • Conserved Sequence
  • DNA Repair Enzymes
  • Evolution, Molecular
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins
  • Peptides / pharmacology
  • Phenotype
  • Protein Structure, Tertiary
  • RNA Precursors / metabolism
  • RNA Splicing Factors
  • RNA Splicing* / drug effects
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / analysis
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Sequence Homology, Amino Acid
  • Spliceosomes / drug effects
  • Spliceosomes / metabolism*
  • Ubiquitin-Protein Ligases / chemistry
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / physiology*


  • Nuclear Proteins
  • PRP19 protein, S cerevisiae
  • Peptides
  • RNA Precursors
  • RNA Splicing Factors
  • RNA, Messenger
  • RNA-Binding Proteins
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin-Protein Ligases
  • DNA Repair Enzymes
  • PRPF19 protein, human