TY  - JOUR
A1  - Grillari, Johannes
A1  - Ajuh, Paul
A1  - Stadler, Guido
A1  - Löscher, Marlies
A1  - Voglauer, Regina
A1  - Ernst, Wolfgang
A1  - Chusainow, Janet
A1  - Eisenhaber, Frank
A1  - Pokar, Marion
A1  - Fortschegger, Klaus
A1  - Grey, Martin
A1  - Lamond, Angus I.
A1  - Katinger, Hermann
T1  - SNEV is an evolutionarily conserved splicing factor whose oligomerization is necessary for spliceosome assembly
T2  - Nucleic Acids Research
N2  - 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.
Y1  - 2005
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/2811
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-26022
N1  - © The Author 2005. The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org
VL  - 33
IS  - 21
SP  - 6868
EP  - 6883
ER  -