GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:16332694

From GONUTS
Jump to: navigation, search
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

Significance

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


See also

References

See Help:References for how to manage references in GONUTS.