Phosphoinositides are a family of lipid signalling molecules that regulate many 
cellular functions in eukaryotes. Phosphatidylinositol-4,5-bisphosphate 
(PtdIns4,5P2), the central component in the phosphoinositide signalling 
circuitry, is generated primarily by type I phosphatidylinositol 4-phosphate 
5-kinases (PIPKIalpha, PIPKIbeta and PIPKIgamma). In addition to functions in 
the cytosol, phosphoinositides are present in the nucleus, where they modulate 
several functions; however, the mechanism by which they directly regulate 
nuclear functions remains unknown. PIPKIs regulate cellular functions through 
interactions with protein partners, often PtdIns4,5P2 effectors, that target 
PIPKIs to discrete subcellular compartments, resulting in the spatial and 
temporal generation of PtdIns4,5P2 required for the regulation of specific 
signalling pathways. Therefore, to determine roles for nuclear PtdIns4,5P2 we 
set out to identify proteins that interacted with the nuclear PIPK, PIPKIalpha. 
Here we show that PIPKIalpha co-localizes at nuclear speckles and interacts with 
a newly identified non-canonical poly(A) polymerase, which we have termed 
Star-PAP (nuclear speckle targeted PIPKIalpha regulated-poly(A) polymerase) and 
that the activity of Star-PAP can be specifically regulated by PtdIns4,5P2. 
Star-PAP and PIPKIalpha function together in a complex to control the expression 
of select mRNAs, including the transcript encoding the key cytoprotective enzyme 
haem oxygenase-1 (refs 8, 9) and other oxidative stress response genes by 
regulating the 3'-end formation of their mRNAs. Taken together, the data 
demonstrate a model by which phosphoinositide signalling works in tandem with 
complement pathways to regulate the activity of Star-PAP and the subsequent 
biosynthesis of its target mRNA. The results reveal a mechanism for the 
integration of nuclear phosphoinositide signals and a method for regulating gene 
expression.