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

Johannes Grillari (Lead / Corresponding author), Paul Ajuh, Guido Stadler, Marlies Löscher, Regina Voglauer, Wolfgang Ernst, Janet Chusainow, Frank Eisenhaber, Marion Pokar, Klaus Fortschegger, Martin Grey, Angus I. Lamond, Hermann Katinger

    Research output: Contribution to journalArticle

    42 Citations (Scopus)

    Abstract

    We have isolated the human protein SNEV as down-regulated 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 homooligomerization of SNEV in HeLa nuclear extract is essential for spliceosome assembly and that it might also be important for spliceosome stability.

    Original languageEnglish
    Pages (from-to)6868-6883
    Number of pages16
    JournalNucleic Acids Research
    Volume33
    Issue number21
    DOIs
    Publication statusPublished - 1 Nov 2005

    Fingerprint Dive into the research topics of 'SNEV is an evolutionarily conserved splicing factor whose oligomerization is necessary for spliceosome assembly'. Together they form a unique fingerprint.

  • Cite this

    Grillari, J., Ajuh, P., Stadler, G., Löscher, M., Voglauer, R., Ernst, W., Chusainow, J., Eisenhaber, F., Pokar, M., Fortschegger, K., Grey, M., Lamond, A. I., & Katinger, H. (2005). SNEV is an evolutionarily conserved splicing factor whose oligomerization is necessary for spliceosome assembly. Nucleic Acids Research, 33(21), 6868-6883. https://doi.org/10.1093/nar/gki986