Published online 6 December 2005
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SNEV is an evolutionarily conserved splicing factor whose oligomerization is necessary for spliceosome assembly
1Institute of Applied Microbiology, University of Natural Resources and Applied Life Sciences Vienna, Austria Muthgasse 18, A-1190 Vienna 2Division of Gene Regulation and Expression, Wellcome Trust Biocentre University of Dundee Dow Street, DD15EH Dundee, UK 3Institute of Molecular Pathology Dr. Bohr-Gasse 7, A-1030 Vienna, Austria 4BMT Research Vienna, Austria 5J.W. Goethe-University, Institute for Microbiology Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany
*To whom correspondence should be addressed. Tel: +43 1 36006 6231; Fax: +43 1 3697615; Email: j.grillari{at}iam.boku.ac.at
Received September 13, 2005. Revised November 11, 2005. Accepted November 11, 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.
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