Abstract
The many functions of phosphoinositides in cytosolic signaling were extensively studied; however, their activities in the cell nucleus are much less clear. In this review, we summarize data about their nuclear localization and metabolism, and review the available literature on their involvements in chromatin remodeling, gene transcription, and RNA processing. We discuss the molecular mechanisms via which nuclear phosphoinositides, in particular phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2), modulate nuclear processes. We focus on PI(4,5)P2’s role in the modulation of RNA polymerase I activity, and functions of the nuclear lipid islets—recently described nucleoplasmic PI(4,5)P2-rich compartment involved in RNA polymerase II transcription. In conclusion, the high impact of the phosphoinositide–protein complexes on nuclear organization and genome functions is only now emerging and deserves further thorough studies.
Highlights
Phosphatidylinositol (PI) is a negatively charged glycerol-based phospholipid with a hydrophobic acyl tail and a hydrophilic inositol head
How are amphipathic phosphoinositides retained in the hydrophilic intranuclear environment? We recently showed that PI(4,5)P2 localizes to a specific, only recently described nuclear compartment—nuclear lipid islets (NLIs) (Figure 2)
PI(4,5)P2 binding promotes conformational changes in PHF8, represses its H3K9me2 demethylase activity and, regulates expression of pre-rRNA genes [79] (Figure 3). All these data indicate that phosphoinositides play multiple specific roles in the nuclear processes depending on their binding partners and physiological state of a cell
Summary
Phosphatidylinositol (PI) is a negatively charged glycerol-based phospholipid with a hydrophobic acyl tail and a hydrophilic inositol head. The hydrophobic acyl tail composition depends on the organism, as well as the tissue. All the stearic acid is linked to position sn-1, and all the arachidonic acid is linked to position sn-2. The main tail composition is of palmitic acid, which is the main saturated fatty acid in position sn-1, while linoleic and linolenic acids are the main unsaturated components in position sn-2. Are nuclear phosphoinositides synthesized within the nucleus or transported to this compartment to this compartment from the cytoplasm? PI(4,5)P2, which was we address these questions with a special emphasis on PI(4,5)P2, which was identified as an important identified as an important regulator of a wide range of nuclear processes.
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