Nuclear phosphoinositide signaling regulates messenger RNA export

Messenger RNA export from the nucleus to the cytoplasm plays an essential role in linking transcription to translation and consequently regulation of protein expression. mRNA export requires a series of events: pre-mRNA processing, ribonucleoprotein targeting to the NPC (nuclear pore complexes), and translocation through nuclear pores to the cytoplasm. Interestingly, the conventional nuclear export machinery, exportins and the Ran GTPase, is not required for mRNA export. Instead, a protein complex consisting of a number of RNA binding proteins is essential for this event including the Aly/REF protein. Phosphoinositide signaling regulates a variety of cellular functions including pre-mRNA splicing and mRNA export. In fact, a phospholipase C-dependent inositol polyphosphate kinase pathway is required for efficient mRNA export. Recently, we showed that Aly is a physiological target of nuclear phosphoinositide-3-kinase (PI3K) signaling, which regulates Aly localization as well as Aly function in cell proliferation and mRNA export through nuclear Akt-mediated phosphorylation and phosphoinositide association. Hence, water-soluble inositol polyphosphates and phosphatidylinositol lipids play pivotal roles in modulating mRNA export.