PMID:16332694

Citation	Grillari, J, Ajuh, P, Stadler, G, Löscher, M, Voglauer, R, Ernst, W, Chusainow, J, Eisenhaber, F, Pokar, M, Fortschegger, K, Grey, M, Lamond, AI and Katinger, H (2005) SNEV is an evolutionarily conserved splicing factor whose oligomerization is necessary for spliceosome assembly. Nucleic Acids Res. 33:6868-83
Abstract	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.
Links	PubMed PMC1310963 Online version:10.1093/nar/gki986
Keywords	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/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
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:CDC5L	located_in	GO:0016607: nuclear speck	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:PRP19	located_in	GO:0016607: nuclear speck	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:PRP19	involved_in	GO:0000245: spliceosomal complex assembly	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:PRP19	enables	GO:0042802: identical protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:Q9UMS4	F		Seeded From UniProt	complete
HUMAN:CDC5L	part_of	GO:0016607: nuclear speck	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete

References

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