The Novel Poly(A) Polymerase Star‐PAP Is Associated With and Phosphorylated by the Protein Kinase CKIα That is Also Required For Expression Of Select Star‐PAP Target mRNAs

We have recently identified Star-PAP, a new nuclear poly(A) polymerase that associates with the PIP kinase phosphatidylinositol 4-phosphate 5-kinase Iα, (PIPKIα) that is required for the expression of a specific subset of mRNAs. Star-PAP activity is directly modulated by the PIPKIα product phosphatidylinositol-4,5-bisphosphate(PI4,5P2), linking nuclear phosphoinositide signaling to gene expression. Here we show that a PI4,5P2 dependent protein kinase activity is also a part of the Star-PAP protein complex. We identify the PI4,5P2 sensitive kinase CKIα as a protein kinase responsible for this activity, and further show that CKIα is capable of directly phosphorylating Star-PAP. Both CKIα and PIPKIα are required for the synthesis of some but not all Star-PAP target mRNA and like Star-PAP, CKIα is associated with these messages in vivo. Taken together, these data indicate that CKIα, PIPKIα 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.