Phosphoinositide turnover regulates multiple cellular processes. Compared with their well-known cytosolic roles, limited information is available on the functions of nuclear phosphoinositides. Here, we show that phosphatidylinositol(4,5)-bisphosphate (PtdIns(4,5)P-2) stably associates with electron-dense particles within the nucleus that resemble interchromatin granule clusters. These PtdIns(4,5)P-2-containing structures have a distribution which is cell-cycle dependent and contain components of both the transcriptional and pre-mRNA processing machinery, including RNA polymerase It and the splicing factor SC-35. Immunodepletion and add-back experiments demonstrate that PtdIns(4,5)P-2 and associated factors are necessary but not sufficient for pre-mRNA splicing in vitro, indicating a crucial role for PtdIns(4,5)P-2-containing complexes in nuclear pre-mRNA processing
