Functional interaction between PIPKIalpha and the non-canonical poly(A) polymerase star-PAP for the efficient 3' end formation of select mRNAs

Phosphoinositides are a family of lipid signalling molecules that act to regulate a number of cellular functions. By identifying proteins which interact with phosphoinositide generating enzymes, great strides have been made revealing mechanisms for phosphoinositide signalling events. This study was undertaken to determine mechanisms for the nuclear phosphoinositide signalling pathways that require the phosphoinositide kinase PIPKIalpha and its product PI4,5P2.;Star-PAP was identified as a direct interacting protein with PIPKIalpha and the enzyme activity of Star-PAP is regulated by PI4,5P2. Star-PAP embodies a unique architecture and its domain arrangement is distinct compared to any known nucleotidyl transferase enzyme. Star-PAP resides in a large protein complex that contains a number of factors required for the 3' end processing of mRNAs, though is devoid of detectable canonical PAP. Unlike the canonical PAP complex, Star-PAP contains PIPKIalpha which is enzymatically active, as well as the phosphoinositide sensitive protein kinase Casein Kinase Ialpha, defining a unique phosphoinositide nuclear complex that is acts to regulate select gene expression.;The collected data to be presented define molecular mechanisms for the regulation of 3' end mRNA processing regulated by nuclear phosphoinositides and demonstrates that nuclear phosphoinositide based signalling pathways function to regulate mRNA levels through controlling 3' end formation of mRNA processing.