CKIalpha is associated with and phosphorylates star-PAP and is also required for expression of select star-PAP target messenger RNAs

We have recently identified Star-PAP, a nuclear poly(A) polymerase that associates with phosphatidylinositol-4-phosphate 5-kinase Ialpha (PIPKIalpha) and is required for the expression of a specific subset of mRNAs. Star-PAP activity is directly modulated by the PIPKIalpha product phosphatidylinositol 4,5-bisphosphate (PI-4,5-P(2)), linking nuclear phosphoinositide signaling to gene expression. Here, we show that PI-4,5-P(2)-dependent protein kinase activity is also a part of the Star-PAP protein complex. We identify the PI-4,5-P(2)-sensitive Casein Kinase Ialpha (CKIalpha) as a protein kinase responsible for this activity and further show that CKIalpha is capable of directly phosphorylating Star-PAP. Both CKIalpha and PIPKIalpha are required for the synthesis of some but not all Star-PAP target mRNA, and like Star-PAP, CKIalpha is associated with these messages in vivo. Taken together, these data indicate that CKIalpha, PIPKIalpha, and Star-PAP function together to modulate the production of specific Star-PAP messages. The Star-PAP complex therefore represents a location where multiple signaling pathways converge to regulate the expression of specific mRNAs.