FISSION YEAST MITOTIC REGULATOR DSK1 IS AN SR PROTEIN-SPECIFIC KINASE

Intricate interplay may exist between pre-mRNA splicing and the cell d ivision cycle, and fission yeast Dsk1 appears to play a role in such a connection, Previous genetic analyses have implicated Dsk1 in the reg ulation of chromosome segregation at the metaphase/anaphase transition , Yet, its protein sequence suggests that Dsk1 may function as a kinas e specific for SR proteins, a family of pre-mRNA splicing factors cont aining arginine-serine repeats, Using an in vitro system with purified components, we showed that Dsk1 phosphorylated human and yeast SR pro teins with high specificity, The Dsk1-phosphorylated SF2/ASF protein w as recognized strongly by a monoclonal antibody (mAb104) known to bind the in vivo phosphoepitope shared by SR proteins, indicating that the phosphorylation sites resided in the RS domain, Moreover, the fission yeast U2AF65 homolog, Prp2/Mis11 protein, was phosphorylated more eff iciently by Dsk1 than by a human SR protein-specific kinase, SRPK1, Th us, these in vitro results suggest that Dsk1 is a fission yeast SR pro tein-specific kinase, and Prp2/Mis11 is likely an in vivo target for D sk1, Together with previous genetic data, the studies support the noti on that Dsk1 may play a role in coordinating pre-mRNA splicing and the cell division cycle.