Snt309p modulates interactions of Prp19p with its associated components tostabilize the Prp19p-associated complex essential for pre-mRNA splicing

The SNT309 gene was identified via a mutation that causes lethality of cell s in combination with a prp19 mutation. We showed previously that Snt309p i s a component of the Prp19p-associated complex and that Snt309p, like Prp19 p, is associated with the spliceosome immediately after or concomitantly wi th dissociation of U4 from the spliceosome. We show here that extracts prep ared from the SNT309-deleted strain (Delta SNT309) were defective in splici ng but could be complemented by addition of the purified Prp19p-associated complex. Isolation of the Prp19p-associated complex from Delta SNT309 extra cts indicated that the complex was destabilized in the absence of Snt309p a nd dissociated on affinity chromatography, suggesting a role of Snt309p in stabilization of the Prp19p-associated complex, Addition of the affinity-pu rified Prp19p-Snt309p binary complex to Delta SNT309 extracts could reconst itute the Prp19p-associated complex, Genetic analysis further suggests that Snt309p plays a role in modulating interactions of Prp19p with other assoc iated components to facilitate formation of the Prp19p-associated complex. A model for how Snt309p modulates such interactions is proposed.