title: Exo70, a subunit of the exocyst complex, interacts with SNEV(hPrp19/hPso4) and is involved in pre-mRNA splicing.
abstract: The Cdc5L (cell division cycle 5-like) complex is a spliceosomal subcomplex that also plays a role in DNA repair. The complex contains the splicing factor hPrp19, also known as SNEV or hPso4, which is involved in cellular life-span regulation and proteasomal breakdown. In a recent large-scale proteomics analysis for proteins associated with this complex, proteins involved in transcription, cell-cycle regulation, DNA repair, the ubiquitin-proteasome system, chromatin remodelling, cellular aging, the cytoskeleton and trafficking, including four members of the exocyst complex, were identified. In the present paper we report that Exo70 interacts directly with SNEV(hPrp19/hPso4) and shuttles to the nucleus, where it associates with the spliceosome. We mapped the interaction site to the N-terminal 100 amino acids of Exo70, which interfere with pre-mRNA splicing in vitro. Furthermore, Exo70 influences the splicing of a model substrate as well as of its own pre-mRNA in vivo. In addition, we found that Exo70 is alternatively spliced in a cell-type- and cell-age- dependent way. These results suggest a novel and unexpected role of Exo70 in nuclear mRNA splicing, where it might signal membrane events to the splicing apparatus.
authors.affiliation: Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria.
authors.forename: Hanna
authors.initials: H
authors.lastname: Dellago
authors.forename: Marlies
authors.initials: M
authors.lastname: Löscher
authors.forename: Paul
authors.initials: P
authors.lastname: Ajuh
authors.forename: Ursula
authors.initials: U
authors.lastname: Ryder
authors.forename: Christian
authors.initials: C
authors.lastname: Kaisermayer
authors.forename: Regina
authors.initials: R
authors.lastname: Grillari-Voglauer
authors.forename: Klaus
authors.initials: K
authors.lastname: Fortschegger
authors.forename: Stefan
authors.initials: S
authors.lastname: Gross
authors.forename: Anna
authors.initials: A
authors.lastname: Gstraunthaler
authors.forename: Nicole
authors.initials: N
authors.lastname: Borth
authors.forename: Frank
authors.initials: F
authors.lastname: Eisenhaber
authors.forename: Angus I
authors.initials: AI
authors.lastname: Lamond
authors.forename: Johannes
authors.initials: J
authors.lastname: Grillari
mesh_terms: D017398:Alternative Splicing; D015153:Blotting, Western; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012322:RNA Precursors / Q000235:genetics*; D000072260:RNA Splicing Factors; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017381:Spliceosomes / Q000235:genetics*; D020798:Two-Hybrid System Techniques; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: C547754:EXOC7 protein, human; D009687:Nuclear Proteins; D012322:RNA Precursors; D000072260:RNA Splicing Factors; D012333:RNA, Messenger; D033921:Vesicular Transport Proteins; D045643:DNA Repair Enzymes; C417041:PRPF19 protein, human