Exo70, a subunit of the exocyst complex, interacts with SnevhPrp19/hPso4 and is involved in pre-mRNA splicing

Hanna Dellago , Marlies Löscher , Paul Ajuh , Ursula Ryder , Christian Kaisermayer , Regina Grillari-Voglauer , Klaus Fortschegger , Stefan Gross , Anna Gstraunthaler , Nicole Borth , Frank Eisenhaber , Angus Lamond , Johannes Grillari (1)

1 Department of Biotechnology

The CDC5L 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 4 members of the exocyst complex, were identified. Here we report that Exo70 interacts directly with SNEVhPrp19/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.

Mots clés: Life Sciences

Hanna Dellago, Marlies Löscher, Paul Ajuh, Ursula Ryder, Christian Kaisermayer, et al.. Exo70, a subunit of the exocyst complex, interacts with SnevhPrp19/hPso4 and is involved in pre-mRNA splicing. Biochemical Journal, 2011, 438 (1), pp.81-91. ⟨10.1042/BJ20110183⟩. ⟨hal-00612963⟩