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Inositol pyrophosphate dynamics impact phosphate homeostasis via modulation of RNA 3' processing and transcription termination

ABSTRACT: Inositol pyrophosphate dynamics impact phosphate homeostasis via modulation of RNA 3' processing and transcription termination

PROVIDER: PRJNA524918 | ENA |

REPOSITORIES: ENA

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Inositol pyrophosphate dynamics impact fission yeast phosphate homeostasis via modulation of RNA 3' processing and transcription termination

Project description:This RNA-Seq analysis compares gene expression of the Inositol pyrophosphate phosphatase mutant aps1∆ and Inositol pyrophsophate kinase mutant asp1-D333A contrasting to the WT in the fission yeast S. pombe

2019-06-16 | GSE131237 | GEO

Inositol pyrophosphate dynamics impact phosphate homeostasis via modulation of RNA 3' processing and transcription termination

Project description:Fission yeast phosphate acquisition genes pho1, pho84, and tgp1 are repressed in phosphate-rich medium by transcription of upstream lncRNAs. Here we show phosphate homeostasis is subject to metabolite control by inositol pyrophosphates (IPPs), exerted through the 3'-processing/termination machinery and the Pol2 CTD code. Increasing IP8 (via Asp1 IPP pyrophosphatase mutation) de-represses the PHO regulon and leads to precocious termination of prt lncRNA synthesis. pho1 de-repression by IP8 depends on cleavage-polyadenylation factor (CPF) subunits, termination factor Rhn1, and the Thr4 letter of the CTD code. pho1 de-repression by mutation of the Ser7 CTD letter depends on IP8. Simultaneous inactivation of Asp1 and Aps1 pyrophosphatases (i.e., too much IP8) is lethal, but this lethality is suppressed by mutations of CPF subunits Ppn1, Swd22, Ssu72, and Ctf1 and CTD mutation T4A. Failure to synthesize IP8 (via Asp1 IPP kinase mutation) results in pho1 hyper-repression. Synthetic lethality of asp1∆ with Ppn1, Swd22, and Ssu72 mutations argues that IP8 plays an important role in essential 3'-processing/termination events, albeit in a manner genetically redundant to CPF. Transcriptional profiling delineates an IPP-responsive regulon composed of genes overexpressed when IP8 levels are increased. Our results establish a novel role for IPPs in cell physiology.

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Inositol pyrophosphate dynamics impact fission yeast phosphate homeostasis via modulation of RNA 3' processing and transcription termination

Project description:Inositol pyrophosphate dynamics impact fission yeast phosphate homeostasis via modulation of RNA 3' processing and transcription termination

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Inositol pyrophosphate InsP8 acts as intracellular phosphate signal in Arabidopsis

Project description:Inositol pyrophosphate InsP8 acts as intracellular phosphate signal in Arabidopsis

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Inositol pyrophosphate InsP8 acts as intracellular phosphate signal in Arabidopsis

Project description:The maintenance of cellular phosphate (Pi) homeostasis is of paramount importance in living organisms. Little is known about how cells sense intracellular Pi status in multi-cellular eukaryotes. Here, we report the identification of inositol pyrophosphate InsP8, a ligand that binds to the Pi sensor protein SPX1 to inhibit PHR1, the central regulator of Pi starvation responses in Arabidopsis. The concentration of InsP8, synthesized by diphosphoinositol pentakisphosphate kinases VIH1 and VIH2, depends on cellular Pi level and the double mutants accumulated higher amounts of Pi. The paradox of Pi toxicity and induction of Pi starvation inducible genes indicated that the cells could not sense cellular Pi without InsP8. Our study reveals that InsP8 acts as a Pi signaling molecule and binds to the receptor SPX1 to regulate Pi homeostasis.

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Inositol pyrophosphates impact phosphate homeostasis via modulation of RNA 3' processing and transcription termination.

Project description: Not available

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SPX domain proteins are agents of inositol pyrophosphate toxicosis in fission yeast

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Project description:Intracellular signaling is conserved in eukaryotes to allow for response to extracellular signals and to regulate development and cellular functions. In fungi, inositol phosphate signaling has been shown to be involved in growth, sexual reproduction, and metabolic adaptation lacking, however, reports of mushroom forming fungi so far. In Schizophyllum commune, an inositol monophosphatase has been found up-regulated during sexual development. The enzyme is crucial for inositol cycling where it catalyzes the last step of inositol phosphate metabolism restoring the inositol pool from the monophosphorylated inositol monophosphate. We overexpressed the gene in this model basidiomycete and verified its involvement in cell wall integrity and intracellular trafficking. Strong phenotypes in mushroom formation and cell metabolism were evidenced by proteome analyses. In addition, altered inositol signaling was shown to be involved in tolerance towards cesium and zinc, and increased metal tolerance towards cadmium, associated with induced expression of kinases and repression of phosphatases within the inositol cycle. The presence of the heavy metals Sr, Cs, Cd, and Zn lowered intracellular calcium levels. We could develop a model integrating inositol signaling in the known signal transduction pathways governed by Ras, G-protein coupled receptors, cAMP and elucidate different roles in development.

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Structural basis for an inositol pyrophosphate kinase surmounting phosphate crowding.

Project description: Not available

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