The novel poly(A) polymerase Star-PAP is a signal-regulated switch at the 3′-end of mRNAs

Li, Weimin; Laishram, Rakesh S.; Anderson, Richard A.

doi:10.1016/j.jbior.2012.10.004

Cited by 26 publications

(26 citation statements)

References 60 publications

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“…Moreover, in the nucleus, PtdIns(4,5) P 2 regulates the activity of a poly(A) polymerase, termed Star-PAP (nuclear speckle targeted PIPKIalpha regulated-poly(A) polymerase) to selectively control the expression of some targeted genes [101]. In humans, PtdIns(4,5) P 2 plays also a major role in regulating various signaling pathways, namely because of the rapid switching it can undergo thanks to the different PPIn kinases and phosphatases using it as a substrate (Figure 1).…”

Section: Ptdins(45)p2 a Phosphoinositide Involved In Actin Dynammentioning

confidence: 99%

Phosphoinositides, Major Actors in Membrane Trafficking and Lipid Signaling Pathways

Craene

Bertazzi

Bär

et al. 2017

IJMS

162

147

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Abstract:Phosphoinositides are lipids involved in the vesicular transport of proteins and lipids between the different compartments of eukaryotic cells. They act by recruiting and/or activating effector proteins and thus are involved in regulating various cellular functions, such as vesicular budding, membrane fusion and cytoskeleton dynamics. Although detected in small concentrations in membranes, their role is essential to cell function, since imbalance in their concentrations is a hallmark of many cancers. Their synthesis involves phosphorylating/dephosphorylating positions D3, D4 and/or D5 of their inositol ring by specific lipid kinases and phosphatases. This process is tightly regulated and specific to the different intracellular membranes. Most enzymes involved in phosphoinositide synthesis are conserved between yeast and human, and their loss of function leads to severe diseases (cancer, myopathy, neuropathy and ciliopathy).Keywords: lipids; membrane trafficking; vesicles; phosphoinositides; phosphatase; kinase Phosphoinositides in Cellular Membranes Lipids, Major Membrane ComponentsThe dynamic modulation of the physicochemical properties of membranes is required for eukaryotic cells function. Indeed, cells live in an environment characterized by temperature, relative humidity, pH, sun exposure, osmotic pressure and nutrient variations. Living organisms have to adapt to variations of these different factors in order to keep their intracellular balance. Eukaryotic cells have achieved this by adopting a compartmentalized organization, which minimizes the intracellular variations resulting from extracellular fluctuations. The plasma membrane is the first barrier separating the cytoplasm from the extracellular medium. Its composition ensures a mechanical protection, but also allows exchanges with the medium through transporters and receptors, as a form of very selective permeability.Membranes are composed of two phospholipid leaflets organized as a bilayer in which sterols, glycolipids and proteins are inserted. The phospholipids of this bilayer are amphiphilic with a hydrophilic group (head) linked to a hydrophobic group (tail) ( Figure 1A). In the bilayer, the hydrophobic groups face each other, thus creating a hydrophobic space in between them, which ensures its role as a barrier. This property is very important for the anchoring of hydrophobic molecules, such as sterols or ceramides, transmembrane domains or the lipid anchor of proteins. The lipid composition of membranes varies according to the organism (eukaryotes or prokaryotes), the cell type (among the different tissues of a multicellular organism), the membrane type (plasma Int.

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Section: Ptdins(45)p2 a Phosphoinositide Involved In Actin Dynammentioning

confidence: 99%

Phosphoinositides, Major Actors in Membrane Trafficking and Lipid Signaling Pathways

Craene

Bertazzi

Bär

et al. 2017

IJMS

162

147

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“…PIPKIα specifically associates with the PI4,5P 2 effector Star-PAP (for S peckle T argeted P IPKIα R egulated- P oly( A ) P olymerase, a non-canonical poly(A) polymerase (PAP), that is critical for the 3’ cleavage, polyadenylation and expression of select mRNAs [183, 195]. Sufficient evidence indicates that PIPKIα, PI4,5P 2 and Star-PAP function together in a complex to control the mRNA processing and expression of select mRNAs [182, 183, 196].…”

Section: Pip Kinases Regulate Pi45p2 Effectors In the Nucleusmentioning

confidence: 99%

“…This again highlights the paradigm where PIPKIs define the specificity of PI4,5P 2 signaling by associating with PI4,5P 2 effectors, in this case PKCδ. The collaborative roles for PIPKIα, PI4,5P 2 , and PKCδ in Star-PAP control of DNA damage induced expression of the apoptotic gene BIK [182, 195] (Figure 4). …”

Section: Pip Kinases Regulate Pi45p2 Effectors In the Nucleusmentioning

confidence: 99%

“…Although the PIPKIα-mediated PI4,5P 2 signaling specifically modulates Star-PAP activity, not all Star-PAP targeting mRNAs are regulated by PIPKIα [183, 195, 202]. It is likely that other nuclear speckle targeted PIP kinases such as PIPKIγi4 or nuclear PIPKII isoforms may control additional Star-PAP target mRNAs.…”

Section: Pip Kinases Regulate Pi45p2 Effectors In the Nucleusmentioning

confidence: 99%

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PIP kinases define PI4,5P2 signaling specificity by association with effectors

Choi

Thapa

Tan

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Phosphatidylinositol 4,5-bisphosphate (PI4,5P2) is an essential lipid messenger with roles in all eukaryotes and most aspects of human physiology. By controlling the targeting and activity of its effectors, PI4,5P2 modulates processes, such as cell migration, vesicular trafficking, cellular morphogenesis, signaling and gene expression. In cells, PI4,5P2 has a much higher concentration than other phosphoinositide species and its total content is largely unchanged in response to extracellular stimuli. The discovery of a vast array of PI4,5P2 binding proteins is consistent with data showing that the majority of cellular PI4,5P2 is sequestered. This supports a mechanism where PI4,5P2 functions as a localized and highly specific messenger. Further support of this mechanism comes from the de novo synthesis of PI4,5P2 which is often linked with PIP kinase interaction with PI4,5P2 effectors and is a mechanism to define specificity of PI4,5P2 signaling. The association of PI4,5P2-generating enzymes with PI4,5P2 effectors regulate effector function both temporally and spatially in cells. In this review, the PI4,5P2 effectors whose functions are tightly regulated by associations with PI4,5P2-generating enzymes will be discussed.

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“…Moreover, the reported presence of PI(4)P5Ks, one of the two key enzymes in PtdIns(4,5) P 2 production, in the nucleus seems to underscore the pivotal importance of PtdIns(4,5) P 2 in nuclear functions. Interestingly, the PI(4)P5KIα and its product PtdIns(4,5) P 2 are suggested to take part in transcription control of certain types of genes through their interaction with poly(A) polymerase termed ‘Star-PAP’ in the nucleus 21 , 43 . Recent studies also indicate the presence of PI(5)P and its metabolizing enzyme PI(5)P4Ks in the nucleus, 12 , 14 , 16 , 44 , 45 thereby demonstrating the widespread expression of a variety of PI kinases in the nucleus.…”

Section: Discussionmentioning

confidence: 99%

Localization and projected role of phosphatidylinositol 4-kinases IIα and IIβ in inositol 1,4,5-trisphosphate-sensitive nucleoplasmic Ca²⁺store vesicles

Yoo¹,

Huh

et al. 2014

Nucleus

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Phosphatidylinositol (PI) kinases are key molecules that participate in the phosphoinositide signaling in the cytoplasm. Despite the accumulating evidence that supports the existence and operation of independent PI signaling system in the nucleus, the exact location of the PI kinases inside the nucleus is not well defined. Here we show that PI4-kinases IIα and IIβ, which play central roles in PI(4,5)P2 synthesis and PI signaling, are localized in numerous small nucleoplasmic vesicles that function as inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)-sensitive Ca2+ stores. This is in accord with the past results that showed the localization of PI4(P)5-kinases that are essential in PI(4,5)P2 production and PI(4,5)P2 in nuclear matrix. Along with PI(4,5)P2 that also exists on the nucleoplasmic vesicle membranes, the localization of PI4-kinases IIα and IIβ in the nucleoplasmic vesicles strongly implicates the vesicles to the PI signaling as well as the Ins(1,4,5)P3-depenent Ca2+ signaling in the nucleus. Accordingly, the nucleoplasmic vesicles indeed release Ca2+ rapidly in response to Ins(1,4,5)P3. Further, the Ins(1,4,5)P3-induced Ca2+ release studies suggest that PI4KIIα and IIβ are localized near the Ins(1,4,5)P3 receptor (Ins(1,4,5)P3R)/Ca2+ channels on the Ca2+ store vesicle membranes. In view of the widespread presence of the Ins(1,4,5)P3-dependent Ca2+ store vesicles and the need to fine-control the nuclear Ca2+ concentrations at multiple sites along the chromatin fibers in the nucleus, the existence of the key PI enzymes in the Ins(1,4,5)P3-dependent nucleoplasmic Ca2+ store vesicles appears to be in perfect harmony with the physiological roles of the PI kinases in the nucleus.

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The novel poly(A) polymerase Star-PAP is a signal-regulated switch at the 3′-end of mRNAs

Cited by 26 publications

References 60 publications

Phosphoinositides, Major Actors in Membrane Trafficking and Lipid Signaling Pathways

Phosphoinositides, Major Actors in Membrane Trafficking and Lipid Signaling Pathways

PIP kinases define PI4,5P2 signaling specificity by association with effectors

Localization and projected role of phosphatidylinositol 4-kinases IIα and IIβ in inositol 1,4,5-trisphosphate-sensitive nucleoplasmic Ca²⁺store vesicles

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The novel poly(A) polymerase Star-PAP is a signal-regulated switch at the 3′-end of mRNAs

Cited by 26 publications

References 60 publications

Phosphoinositides, Major Actors in Membrane Trafficking and Lipid Signaling Pathways

Phosphoinositides, Major Actors in Membrane Trafficking and Lipid Signaling Pathways

PIP kinases define PI4,5P2 signaling specificity by association with effectors

Localization and projected role of phosphatidylinositol 4-kinases IIα and IIβ in inositol 1,4,5-trisphosphate-sensitive nucleoplasmic Ca2+store vesicles

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Localization and projected role of phosphatidylinositol 4-kinases IIα and IIβ in inositol 1,4,5-trisphosphate-sensitive nucleoplasmic Ca²⁺store vesicles