Nuclear PtdIns(4,5)P2 assembles in a mitotically regulated particle involved in pre-mRNA splicing.
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)P2) stably associates with electron-dense particles within the nucleus that resemble interchromatin granule clusters. These PtdIns(4,5)P2-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 II and the splicing factor SC-35. Immunodepletion and add-back experiments demonstrate that PtdIns(4,5)P2 and associated factors are necessary but not sufficient for pre-mRNA splicing in vitro, indicating a crucial role for PtdIns(4,5)P2-containing complexes in nuclear pre-mRNA processing.
Osborne
S L
SL
Molecular Neuropathobiology Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK.
Thomas
C L
CL
Gschmeissner
S
S
Schiavo
G
G
D000911:Antibodies, Monoclonal; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008051:Lipid Bilayers; D008938:Mitosis; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism / Q000502:physiology*; D012319:RNA Polymerase II / Q000378:metabolism; D012322:RNA Precursors / Q000502:physiology*; D012326:RNA Splicing
D000911:Antibodies, Monoclonal; D008051:Lipid Bilayers; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D012322:RNA Precursors; D012319:RNA Polymerase II