Inositol polyphosphates: a new frontier for regulating gene expression

Alcázar-Román, Abel R.; Wente, Susan R.

doi:10.1007/s00412-007-0126-4

Cited by 93 publications

(97 citation statements)

References 137 publications

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“…These small nuclear substructures are believed to be to be the sites of storage and/or assembly of pre-mRNA splicing factors. The exact function of PtdIns(4,5)P 2 and PtdIns-PLC in nuclear speckles is currently under investigation, but they are involved in linking the production of diacylglycerol (DAG) and InsP 3 (and their metabolites) to the control of RNA processing (Alcazar-Roman and Wente, 2008). Mammalian cells express at least 13 different PtdIns-PLC isozymes that can be grouped into six subfamilies (β, γ, δ, ε, η and ζ) (Cockcroft, 2006;Suh et al, 2008), of which PtdIns-PLCβ 1 is considered to be the predominant nuclear form Ye and Ahn, 2008).…”

Section: Autonomous Generation Of Ca 2+ -Mobilising Messengers In Thementioning

confidence: 99%

An update on nuclear calcium signalling

Bootman

Fearnley

Smyrnias

et al. 2009

Journal of Cell Science

187

194

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Over the past 15 years or so, numerous studies have sought to characterise how nuclear calcium (Ca 2+ ) signals are generated and reversed, and to understand how events that occur in the nucleoplasm influence cellular Ca 2+ activity, and vice versa. In this Commentary, we describe mechanisms of nuclear Ca 2+ signalling and discuss what is known about the origin and physiological significance of nuclear Ca 2+ transients. In particular, we focus on the idea that the nucleus has an autonomous Ca 2+ signalling system that can generate its own Ca 2+ transients that modulate processes such as gene transcription. We also discuss the role of nuclear pores and the nuclear envelope in controlling ion flux into the nucleoplasm. Journal of Cell Science 2338(which would cause its nuclear export) and through a physical interaction that occludes a nuclear-export sequence (NES) in the NFAT protein.An example of a nuclear-localised transcription factor that is regulated by both nuclear and cytosolic Ca 2+ signals is cyclic AMP response element-binding protein (CREB). The signalling mechanisms that underlie CREB activation have been worked out particularly well in neurons, in which it has been established that depolarisation leads to the rapid phosphorylation of CREB on Ser133 by Ca 2+ -calmodulin-dependent kinase IV, which provides a necessary, but not sufficient, signal for CREB-mediated gene transcription (Dolmetsch et al., 2001). The triggering event is an increase in cytosolic Ca 2+ levels in the immediate vicinity of L-type Ca 2+ channels or N-methyl-D-aspartate receptors that are found in the synapse, at a site that is distal to the nucleus (Shaywitz and Greenberg, 1999). As CREB is only found in the nucleus, the phosphorylation of Ser133 is mediated by one of several Ca 2+ -sensitive signal transduction cascades that convey information from the remote synapses into the nucleus. In the nucleus, phosphorylated CREB binds additional proteins to form a transcriptionally active complex (Shaywitz and Greenberg, 1999). Although the synaptic Ca 2+ signal does not need to propagate to the nucleus to induce phosphorylation of Ser133 on CREB, an increase in the level of nuclear Ca 2+ is required for CREB-mediated gene transcription to occur. This is because additional Ca 2+ -dependent phosphorylation of CREB and its co-activators is required (Chawla et al., 1998;Kornhauser et al., 2002). Indeed, nuclear injection of an artificial Ca 2+ buffer prevents CREB-mediated gene transcription, but not transcription induced by the serum-response element, which is sensitive to cytosolic Ca 2+ buffering (Hardingham et al., 1997).Another well-known target of nuclear Ca 2+ signalling is the transcriptional regulator downstream regulatory element antagonist modulator (DREAM). It is well established that DREAM represses the expression of prodynorphin, an opiate-receptor precursor, and that mice that lack DREAM have a constitutive analgesic condition (Cheng et al., 2002). DREAM contains four Ca 2+ -binding EF hands (a widely expressed structural mo...

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Section: Autonomous Generation Of Ca 2+ -Mobilising Messengers In Thementioning

confidence: 99%

An update on nuclear calcium signalling

Bootman

Fearnley

Smyrnias

et al. 2009

Journal of Cell Science

187

194

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“…Inositol phosphates constitute a family of soluble molecules which play a central role in cell signaling (1)(2)(3). The large variety of inositol phosphate species stems from the attachment of one or more phosphate groups to the six carbon myo-inositol ring.…”

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confidence: 99%

Arginine Transcriptional Response Does Not Require Inositol Phosphate Synthesis

Bosch

Saiardi

2012

Journal of Biological Chemistry

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Background:The involvement of inositol phosphates produced by the yeast inositol-polyphosphate multikinase, Arg82, in transcription is controversial. Results: Catalytically inactive Arg82 restores the regulation of arginine-dependent genes in an ARG82 knock-out. Conclusion: Inositol phosphates do not regulate arginine-dependent gene expression. Significance: Independently of its enzymatic activity Arg82 controls arginine-responsive genes.

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“…IP 6 and other inositol polyphosphates have key roles in gene expression through regulation of chromatin remodeling, transcription factor activation, mRNA editing, mRNA export, and translation (35). Functional in vivo links for IP 6 production have come from using a S. cerevisiae ipk1-null (⌬) mutant that presumably lacks IP 6 as well as its pyrophosphorylation products, with a coincident drastic elevation in levels of inositol phosphates upstream of IP 6 (34,36,37 …”

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confidence: 99%

Control of mRNA Export and Translation Termination by Inositol Hexakisphosphate Requires Specific Interaction with Gle1

Alcázar-Román

Bolger

Wente

2010

Journal of Biological Chemistry

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The unidirectional translocation of messenger RNA (mRNA) through the aqueous channel of the nuclear pore complex (NPC) is mediated by interactions between soluble mRNA export factors and distinct binding sites on the NPC. At the cytoplasmic side of the NPC, the conserved mRNA export factors Gle1 and inositol hexakisphosphate (IP 6 ) play an essential role in mRNA export by activating the ATPase activity of the DEAD-box protein Dbp5, promoting localized messenger ribonucleoprotein complex remodeling, and ensuring the directionality of the export process. In addition, Dbp5, Gle1, and IP 6 are also required for proper translation termination. However, the specificity of the IP 6 -Gle1 interaction in vivo is unknown. Here, we characterize the biochemical interaction between Gle1 and IP 6 and the relationship to Dbp5 binding and stimulation. We identify Gle1 residues required for IP 6 binding and show that these residues are needed for IP 6 -dependent Dbp5 stimulation in vitro. Furthermore, we demonstrate that Gle1 is the primary target of IP 6 for both mRNA export and translation termination in vivo. In Saccharomyces cerevisiae cells, the IP 6 -binding mutants recapitulate all of the mRNA export and translation termination defects found in mutants depleted of IP 6 . We conclude that Gle1 specifically binds IP 6 and that this interaction is required for the full potentiation of Dbp5 ATPase activity during both mRNA export and translation termination.Directional transport of mRNA from the nucleus to the cytoplasm is a highly orchestrated process that bridges nuclear mRNA processing events to protein synthesis in the cytoplasm and thus represents a central step in the regulation of gene expression (1-4). Properly capped, spliced, and polyadenylated mRNAs and their associated RNA-binding proteins constitute mature messenger ribonucleoprotein particles (mRNPs). 4 Of importance for nuclear export, soluble mRNA export factors associate with mRNAs throughout this maturation process, some serving dual roles of mRNA processing and transport regulators (5-8). Export requires targeting to and translocation through NPCs, large hetero-oligomeric structures embedded in nuclear envelope pores. The conserved Saccharomyces cerevisiae Mex67/Mtr2 heterodimer (vertebrate TAP/p15 or NXF1/NXT1) is thought to be the major mRNA export receptor, directly binding the mRNP in the nucleus and facilitating NPC docking and translocation by interaction with NPC proteins (Nups) (1, 9, 10). Mex67-Mtr2 interacts preferentially with phenylalanine-glycine repeats found in Nup domains positioned on the nuclear NPC face and within the central NPC channel (11,12).In addition to critical interactions between Mex67-Mtr2 and phenylalanine-glycine repeat domains in the NPC, directional mRNP export is coincident with altered protein-protein and protein-RNA interactions in the mRNP complex (13). For example, Mex67 and the nuclear poly(A) ϩ -binding protein Nab2 are removed from the mRNP during or after the terminal NPC export step (14, 15). Key factors that med...

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Inositol polyphosphates: a new frontier for regulating gene expression

Cited by 93 publications

References 137 publications

An update on nuclear calcium signalling

An update on nuclear calcium signalling

Arginine Transcriptional Response Does Not Require Inositol Phosphate Synthesis

Control of mRNA Export and Translation Termination by Inositol Hexakisphosphate Requires Specific Interaction with Gle1

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