scholarly journals Genomically hardwired regulation of gene activity orchestrates cellular iron homeostasis in Arabidopsis

Author(s):  
En-Jung Hsieh ◽  
Wendar Lin ◽  
Wolfgang Schmidt

Abstract Iron (Fe) is an essential micronutrient that plays pivotal roles as electron donor and catalyst across organisms. In plants, variable, often insufficient Fe supply necessitates mechanisms that constantly attune Fe uptake rates and recalibrate cellular Fe homeostasis. Here, we show that short-term (0.5, 6, and 12 h) exposure of Arabidopsis thaliana plants to Fe deficiency triggered massive changes in gene activity governed by transcription and alternative splicing (AS), regulatory layers that were to a large extent mutually exclusive. Such preclusion was not observed for genes that are directly involved in the acquisition of Fe, which appears to be concordantly regulated by both expression and AS. Generally, genes with lower splice site strengths and higher intron numbers were more likely to be regulated by AS, no dependence was on gene architecture was observed for transcriptionally controlled genes. Conspicuously, specific processes were associated with particular genomic features and biased towards either regulatory mode, suggesting that genomic hardwiring is functionally biased. Early changes in splicing patterns were, in many cases, congruent with later changes in transcript or protein abundance, thus contributing to the pronounced transcriptome-proteome discordance observed in plants.

2021 ◽  
Author(s):  
En-Jung Hsieh ◽  
Wedar Lin ◽  
Wolfgang Schmidt

Iron (Fe) is an essential micronutrient that plays pivotal roles as electron donor and catalyst across organisms. In plants, variable, often insufficient Fe supply necessitates mechanisms that constantly attune Fe uptake rates and recalibrate cellular Fe homeostasis. Here, we show that short-term (0.5, 6, and 12 h) exposure of Arabidopsis thaliana plants to Fe deficiency triggered massive changes in gene activity governed by transcription and alternative splicing (AS), regulatory layers that were to a large extent mutually exclusive. Such preclusion was not observed for genes that are directly involved in the acquisition of Fe, which appears to be concordantly regulated by both expression and AS. Generally, genes with lower splice site strengths and higher intron numbers were more likely to be regulated by AS, no dependence was on gene architecture was observed for transcriptionally controlled genes. Conspicuously, specific processes were associated with particular genomic features and biased towards either regulatory mode, suggesting that genomic hardwiring is functionally biased. Early changes in splicing patterns were, in many cases, congruent with later changes in transcript or protein abundance, thus contributing to the pronounced transcriptome-proteome discordance observed in plants.


2014 ◽  
Vol 15 (12) ◽  
pp. 1125-1140 ◽  
Author(s):  
Mohsin Raza ◽  
Sankalpa Chakraborty ◽  
Monjoy Choudhury ◽  
Prahlad Ghosh ◽  
Alo Nag

2021 ◽  
Vol 39 (S2) ◽  
Author(s):  
J. Devin ◽  
T. Cañeque ◽  
Y.‐L. Lin ◽  
L. Mondoulet ◽  
J.‐L. Veyrune ◽  
...  

Blood ◽  
2005 ◽  
Vol 105 (5) ◽  
pp. 2161-2167 ◽  
Author(s):  
Guangjun Nie ◽  
Alex D. Sheftel ◽  
Sangwon F. Kim ◽  
Prem Ponka

AbstractCytosolic ferritin sequesters and stores iron and, consequently, protects cells against iron-mediated free radical damage. However, the function of the newly discovered mitochondrial ferritin (MtFt) is unknown. To examine the role of MtFt in cellular iron metabolism, we established a cell line that stably overexpresses mouse MtFt under the control of a tetracycline-responsive promoter. The overexpression of MtFt caused a dose-dependent iron deficiency in the cytosol that was revealed by increased RNA-binding activity of iron regulatory proteins (IRPs) along with an increase in transferrin receptor levels and decrease in cytosolic ferritin. Consequently, the induction of MtFt resulted in a dramatic increase in cellular iron uptake from transferrin, most of which was incorporated into MtFt. The induction of MtFt caused a shift of iron from cytosolic ferritin to MtFt. In addition, iron inserted into MtFt was less available for chelation than that in cytosolic ferritin and the expression of MtFt was associated with decreased mitochondrial and cytosolic aconitase activities, the latter being consistent with the increase in IRP-binding activity. In conclusion, our results indicate that overexpression of MtFt causes a dramatic change in intracellular iron homeostasis and that shunting iron to MtFt likely limits its availability for active iron proteins.


2009 ◽  
Vol 105 (5) ◽  
pp. 801-810 ◽  
Author(s):  
Leonor Ramirez ◽  
Eduardo Julián Zabaleta ◽  
Lorenzo Lamattina

1999 ◽  
Vol 96 (10) ◽  
pp. 5434-5439 ◽  
Author(s):  
L. Salter-Cid ◽  
A. Brunmark ◽  
Y. Li ◽  
D. Leturcq ◽  
P. A. Peterson ◽  
...  

2012 ◽  
Vol 288 (3) ◽  
pp. 1696-1705 ◽  
Author(s):  
Vinay A. Patil ◽  
Jennifer L. Fox ◽  
Vishal M. Gohil ◽  
Dennis R. Winge ◽  
Miriam L. Greenberg

2018 ◽  
Vol 115 (39) ◽  
pp. E9085-E9094 ◽  
Author(s):  
Oliver Stehling ◽  
Jae-Hun Jeoung ◽  
Sven A. Freibert ◽  
Viktoria D. Paul ◽  
Sebastian Bänfer ◽  
...  

Maturation of iron-sulfur (Fe-S) proteins in eukaryotes requires complex machineries in mitochondria and cytosol. Initially, Fe-S clusters are assembled on dedicated scaffold proteins and then are trafficked to target apoproteins. Within the cytosolic Fe-S protein assembly (CIA) machinery, the conserved P-loop nucleoside triphosphatase Nbp35 performs a scaffold function. In yeast, Nbp35 cooperates with the related Cfd1, which is evolutionary less conserved and is absent in plants. Here, we investigated the potential scaffold function of human CFD1 (NUBP2) in CFD1-depleted HeLa cells by measuring Fe-S enzyme activities or 55Fe incorporation into Fe-S target proteins. We show that CFD1, in complex with NBP35 (NUBP1), performs a crucial role in the maturation of all tested cytosolic and nuclear Fe-S proteins, including essential ones involved in protein translation and DNA maintenance. CFD1 also matures iron regulatory protein 1 and thus is critical for cellular iron homeostasis. To better understand the scaffold function of CFD1-NBP35, we resolved the crystal structure of Chaetomium thermophilum holo-Cfd1 (ctCfd1) at 2.6-Å resolution as a model Cfd1 protein. Importantly, two ctCfd1 monomers coordinate a bridging [4Fe-4S] cluster via two conserved cysteine residues. The surface-exposed topology of the cluster is ideally suited for both de novo assembly and facile transfer to Fe-S apoproteins mediated by other CIA factors. ctCfd1 specifically interacted with ATP, which presumably associates with a pocket near the Cfd1 dimer interface formed by the conserved Walker motif. In contrast, ctNbp35 preferentially bound GTP, implying differential regulation of the two fungal scaffold components during Fe-S cluster assembly and/or release.


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