OsIRO3 Plays an Essential Role in Iron Deficiency Responses and Regulates Iron Homeostasis in Rice

Iron (Fe) homeostasis is essential for plant growth and development, and it is strictly regulated by a group of transcriptional factors. Iron-related transcription factor 3 (OsIRO3) was previously identified as a negative regulator for Fe deficiency response in rice. However, the molecular mechanisms by which OsIRO3 regulate Fe homeostasis is unclear. Here, we report that OsIRO3 is essential for responding to Fe deficiency and maintaining Fe homeostasis in rice. OsIRO3 is expressed in the roots, leaves, and base nodes, with a higher level in leaf blades at the vegetative growth stage. Knockout of OsIRO3 resulted in a hypersensitivity to Fe deficiency, with severe necrosis on young leaves and defective root development. The iro3 mutants accumulated higher levels of Fe in the shoot under Fe-deficient conditions, associated with upregulating the expression of OsNAS3, which lead to increased accumulation of nicotianamine (NA) in the roots. Further analysis indicated that OsIRO3 can directly bind to the E-box in the promoter of OsNAS3. Moreover, the expression of typical Fe-related genes was significantly up-regulated in iro3 mutants under Fe-sufficient conditions. Thus, we conclude that OsIRO3 plays a key role in responding to Fe deficiency and regulates NA levels by directly, negatively regulating the OsNAS3 expression.

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IRON MAN interacts with BRUTUS to maintain iron homeostasis in Arabidopsis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2109063118 ◽

2021 ◽

Vol 118 (39) ◽

pp. e2109063118

Author(s):

Yang Li ◽

Cheng Kai Lu ◽

Chen Yang Li ◽

Ri Hua Lei ◽

Meng Na Pu ◽

...

Keyword(s):

Arabidopsis Thaliana ◽

Transcription Factors ◽

Iron Homeostasis ◽

Fe Deficiency ◽

Small Peptides ◽

Interaction Domain ◽

C Terminus ◽

Positive Regulators ◽

Fe Homeostasis ◽

And Function

IRON MAN (IMA) peptides, a family of small peptides, control iron (Fe) transport in plants, but their roles in Fe signaling remain unclear. BRUTUS (BTS) is a potential Fe sensor that negatively regulates Fe homeostasis by promoting the ubiquitin-mediated degradation of bHLH105 and bHLH115, two positive regulators of the Fe deficiency response. Here, we show that IMA peptides interact with BTS. The C-terminal parts of IMA peptides contain a conserved BTS interaction domain (BID) that is responsible for their interaction with the C terminus of BTS. Arabidopsis thaliana plants constitutively expressing IMA genes phenocopy the bts-2 mutant. Moreover, IMA peptides are ubiquitinated and degraded by BTS. bHLH105 and bHLH115 also share a BID, which accounts for their interaction with BTS. IMA peptides compete with bHLH105/bHLH115 for interaction with BTS, thereby inhibiting the degradation of these transcription factors by BTS. Genetic analyses suggest that bHLH105/bHLH115 and IMA3 have additive roles and function downstream of BTS. Moreover, the transcription of both BTS and IMA3 is activated directly by bHLH105 and bHLH115 under Fe-deficient conditions. Our findings provide a conceptual framework for understanding the regulation of Fe homeostasis: IMA peptides protect bHLH105/bHLH115 from degradation by sequestering BTS, thereby activating the Fe deficiency response.

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Glutathione regulates subcellular iron homeostasis via transcriptional activation of iron responsive genes in Arabidopsis

10.1101/2021.05.09.443283 ◽

2021 ◽

Author(s):

Ranjana Shee ◽

Soumi Ghosh ◽

Pinki Khan ◽

Salman Sahid ◽

Chandan Roy ◽

...

Keyword(s):

Transcription Factors ◽

Transcriptional Activation ◽

Iron Homeostasis ◽

Fe Deficiency ◽

Fe Content ◽

Increased Sensitivity ◽

Fe Homeostasis ◽

Bhlh Transcription Factors ◽

Dependent Pathway

Glutathione (GSH) is a ubiquitous molecule known to regulate various physiological and developmental phenomena in plants. Recently, its involvement in regulating iron (Fe) deficiency response was established in Arabidopsis. However, the role of GSH in modulating subcellular Fe homeostasis remained elusive. In this study, we dissected the role of GSH in regulating Fe homeostasis in Arabidopsis shoots under Fe limited conditions. The two GSH depleted mutants, cad2-1 and pad2-1 displayed increased sensitivity to Fe deficiency with smaller rosette diameter and higher chlorosis level compared with the Col-0 plants. Interestingly, the expression of the vacuolar Fe exporters, AtNRAMP3 and AtNRAMP4, chloroplast Fe importer, AtPIC1, along with AtFer1 and AtIRT1 were significantly down-regulated in these mutants. The expression of these genes were up-regulated in response to exogenous GSH treatment while treatment with BSO, a GSH inhibitor, down-regulated their expression. Moreover, the mutants accumulated higher Fe content in the vacuole and lower in the chloroplast compared with Col-0 under Fe limited condition suggesting a role of GSH in modulating subcellular Fe homeostasis. This regulation was, further, found to involve a GSNO-dependent pathway. Promoter analysis revealed that GSH induced the transcription of these genes presumably via S-nitrosylation of different Fe responsive bHLH transcription factors.

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bHLH11 negatively regulates Fe homeostasis by its EAR motifs recruiting corepressors in Arabidopsis

10.1101/2020.04.09.035097 ◽

2020 ◽

Author(s):

Yang Li ◽

Rihua Lei ◽

Mengna Pu ◽

Yuerong Cai ◽

Chengkai Lu ◽

...

Keyword(s):

Molecular Mechanisms ◽

Signal Sequence ◽

Negative Regulator ◽

Fine Tuning ◽

Nuclear Accumulation ◽

Loss Of Function ◽

Enhanced Sensitivity ◽

Crucial Component ◽

Regulation Function ◽

Fe Homeostasis

ABSTRACTIron (Fe) homeostasis is essential for plant growth and development. Although tremendous progress has been made in understanding the maintenance of Fe homeostasis in plants, the underlying molecular mechanisms remain elusive. Recently, bHLH11 was reported to function as a negative regulator. However, the molecular mechanism by which bHLH11 regulates Fe homeostasis is unclear. Here, we generated two bhlh11 loss-of-function mutants which displayed the enhanced sensitivity to excessive Fe. bHLH11 is located in the cytoplasm and nucleus due to lack of a nuclear location signal sequence, and its interaction partners, bHLH IVc transcription factors (TFs) (bHLH34, bHLH104, bHLH105 and bHLH115) facilitate its nuclear accumulation. bHLH11 exerts its negative regulation function by recruiting the corepressors TOPLESS/TOPLESS-RELATED. Moreover, bHLH11 antagonizes the transactivity of bHLH IVc TFs towards bHLH Ib genes (bHLH38, bHLH39, bHLH100 and bHLH101). This work indicates that bHLH11 is a crucial component of Fe homeostasis signaling network, playing a pivotal role in the fine-tuning of Fe homeostasis.

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Annotation and Molecular Characterisation of the TaIRO3 and TaHRZ Iron Homeostasis Genes in Bread Wheat (Triticum aestivum L.)

Genes ◽

10.3390/genes12050653 ◽

2021 ◽

Vol 12 (5) ◽

pp. 653

Author(s):

Oscar Carey-Fung ◽

Jesse T. Beasley ◽

Alexander A. T. Johnson

Keyword(s):

Triticum Aestivum ◽

Bread Wheat ◽

Iron Homeostasis ◽

Zinc Finger Protein ◽

Expression Profiles ◽

Diploid Species ◽

Triticum Aestivum L ◽

Fe Deficiency ◽

Pcr Analysis ◽

Fe Homeostasis

Effective maintenance of plant iron (Fe) homoeostasis relies on a network of transcription factors (TFs) that respond to environmental conditions and regulate Fe uptake, translocation, and storage. The iron-related transcription factor 3 (IRO3), as well as haemerythrin motif-containing really interesting new gene (RING) protein and zinc finger protein (HRZ), are major regulators of Fe homeostasis in diploid species like Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa L.), but remain uncharacterised in hexaploid bread wheat (Triticum aestivum L.). In this study, we have identified, annotated, and characterised three TaIRO3 homoeologs and six TaHRZ1 and TaHRZ2 homoeologs in the bread wheat genome. Protein analysis revealed that TaIRO3 and TaHRZ proteins contain functionally conserved domains for DNA-binding, dimerisation, Fe binding, or polyubiquitination, and phylogenetic analysis revealed clustering of TaIRO3 and TaHRZ proteins with other monocot IRO3 and HRZ proteins, respectively. Quantitative reverse-transcription PCR analysis revealed that all TaIRO3 and TaHRZ homoeologs have unique tissue expression profiles and are upregulated in shoot tissues in response to Fe deficiency. After 24 h of Fe deficiency, the expression of TaHRZ homoeologs was upregulated, while the expression of TaIRO3 homoeologs was unchanged, suggesting that TaHRZ functions upstream of TaIRO3 in the wheat Fe homeostasis TF network.

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Iron deficiency induced changes in Fe homeostasis and 14-3-3 interactomics of Arabidopsis thaliana

10.21203/rs.3.rs-445322/v1 ◽

2021 ◽

Author(s):

Jing Gao ◽

Paula J. M. Kleeff ◽

Ka Wan Li ◽

Albertus H. Boer

Keyword(s):

Arabidopsis Thaliana ◽

Sufficient Conditions ◽

Tca Cycle ◽

Fe Deficiency ◽

Functional Aspects ◽

Clear Explanation ◽

Fe Uptake ◽

Physiological Analysis ◽

Fe Homeostasis ◽

Induced Changes

Abstract Members of 14-3-3 protein family are involved in the proper operation of Fe acquisition mechanisms at physiological and gene expression levels in Arabidopsis thaliana. To more directly and effectively observe whether members of 14-3-3 non-epsilon group have a function in Fe-deficiency adaptation, three higher order quadruple KOs, kappa/lambda/phi/chi (klpc), kappa/lambda/upsilon/nu(klun), and upsilon/nu/phi/chi (unpc) were generated and applied for physiological analysis in this study. The mutant plants that combine kl with un (klun) or kl with pc (klpc) mutations showed a better Fe uptake than Wt plants at low medium Fe, while this phenotype was absent in unpc mutant. The higher Fe uptake by klun correlated with a higher Fe-deficiency induced expression of selected Fe-related genes. The dynamics of 14-3-3-client interactions analysis showed that a subset of 27 proteins differentially interacted with 14-3-3 in roots caused by Fe deficiency. Many of these Fe responsive proteins have a role in glycolysis and TCA cycle, the FoF1-synthase and in the cysteine/methionine synthesis. Also, the 14-3-3 interactome of the klun roots showed significant differences with that of Wt roots under Fe sufficient conditions, where most of these differential binding proteins showed enhanced binding in the klun mutant. Nevertheless, a clear explanation for the observed phenotypes awaits a more detailed analysis of the functional aspects of 14-3-3 binding to the target proteins identified in this study.

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Mechanisms underlying iron deficiency-induced resistance against pathogens with different lifestyles

Journal of Experimental Botany ◽

10.1093/jxb/eraa535 ◽

2020 ◽

Cited By ~ 1

Author(s):

Pauline L Trapet ◽

Eline H Verbon ◽

Renda R Bosma ◽

Kirsten Voordendag ◽

Johan A Van Pelt ◽

...

Keyword(s):

Induced Resistance ◽

Pseudomonas Syringae ◽

Sufficient Conditions ◽

Fe Deficiency ◽

Systemic Resistance ◽

Mineral Nutrient ◽

Wild Type ◽

Starvation Stress ◽

Fe Homeostasis ◽

Hyaloperonospora Arabidopsidis

Abstract Iron (Fe) is a poorly available mineral nutrient which affects the outcome of many cross-kingdom interactions. In Arabidopsis thaliana, Fe starvation limits infection by necrotrophic pathogens. Here, we report that Fe deficiency also reduces disease caused by the hemi-biotrophic bacterium Pseudomonas syringae and the biotrophic oomycete Hyaloperonospora arabidopsidis, indicating that Fe deficiency-induced resistance is effective against pathogens with different lifestyles. Furthermore, we show that Fe deficiency-induced resistance is not caused by withholding Fe from the pathogen but is a plant-mediated defense response that requires activity of ethylene and salicylic acid. Because rhizobacteria-induced systemic resistance (ISR) is associated with a transient up-regulation of the Fe deficiency response, we tested whether Fe deficiency-induced resistance and ISR are similarly regulated. However, Fe deficiency-induced resistance functions independently of the ISR regulators MYB72 and BGLU42, indicating that both types of induced resistance are regulated in a different manner. Mutants opt3 and frd1, which display misregulated Fe homeostasis under Fe-sufficient conditions, show disease resistance levels comparable with those of Fe-starved wild-type plants. Our results suggest that disturbance of Fe homeostasis, through Fe starvation stress or other non-homeostatic conditions, is sufficient to prime the plant immune system for enhanced defense.

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FER-LIKE FE DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (OsFIT) interacts with OsIRO2 to regulate iron homeostasis

10.1101/2020.03.06.981126 ◽

2020 ◽

Author(s):

Gang Liang ◽

Huimin Zhang ◽

Yang Li ◽

Mengna Pu ◽

Yujie Yang ◽

...

Keyword(s):

Transcription Factor ◽

Oryza Sativa ◽

Iron Homeostasis ◽

Transcription Activation ◽

Fe Deficiency ◽

Bhlh Transcription Factor ◽

Loss Of Function ◽

Deficiency Symptoms ◽

Fe Uptake ◽

Fe Homeostasis

ABSTRACTThere are two Fe-uptake strategies for maintaining Fe homeostasis in plants. As a special graminaceous plant, rice applies both strategies. However, it remains unclear how these two strategies are regulated in rice. IRON-RELATED BHLH TRANSCRIPTION FACTOR 2 (OsIRO2) is critical for regulating Fe uptake in rice. In this study, we identified an interacting partner of OsIRO2, Oryza sativa FER-LIKE FE DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (OsFIT), which encodes a bHLH transcription factor. The OsIRO2 protein is localized in the cytoplasm and nucleus, but OsFIT facilitates the accumulation of OsIRO2 in the nucleus. Loss-of-function mutations to OsFIT result in decreased Fe accumulation, severe Fe-deficiency symptoms, and disrupted expression of Fe-uptake genes. In contrast, OsFIT overexpression promotes Fe accumulation and the expression of Fe-uptake genes. Genetic analyses indicated that OsFIT and OsIRO2 function in the same genetic node. Further analysis suggested that OsFIT and OsIRO2 form a functional transcription activation complex to initiate the expression of Fe-uptake genes. Our findings provide a mechanism understanding of how rice maintains Fe homeostasis.One-sentence summaryOsFIT interacts with and facilitates the accumulation of OsIRO2 in the nucleus where the OsFIT-OsIRO2 transcription complex initiates the transcription of Fe deficiency responsive genes.

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Molecular Pathways Involved in the Development of Congenital Erythrocytosis

Genes ◽

10.3390/genes12081150 ◽

2021 ◽

Vol 12 (8) ◽

pp. 1150

Author(s):

Jana Tomc ◽

Nataša Debeljak

Keyword(s):

Signal Transduction ◽

Iron Homeostasis ◽

Molecular Mechanisms ◽

Oxygen Affinity ◽

Molecular Pathways ◽

Disease Development ◽

Post Translational Modifications ◽

Hemoglobin Oxygen Affinity ◽

Insight Into ◽

Idiopathic Erythrocytosis

Patients with idiopathic erythrocytosis are directed to targeted genetic testing including nine genes involved in oxygen sensing pathway in kidneys, erythropoietin signal transduction in pre-erythrocytes and hemoglobin-oxygen affinity regulation in mature erythrocytes. However, in more than 60% of cases the genetic cause remains undiagnosed, suggesting that other genes and mechanisms must be involved in the disease development. This review aims to explore additional molecular mechanisms in recognized erythrocytosis pathways and propose new pathways associated with this rare hematological disorder. For this purpose, a comprehensive review of the literature was performed and different in silico tools were used. We identified genes involved in several mechanisms and molecular pathways, including mRNA transcriptional regulation, post-translational modifications, membrane transport, regulation of signal transduction, glucose metabolism and iron homeostasis, which have the potential to influence the main erythrocytosis-associated pathways. We provide valuable theoretical information for deeper insight into possible mechanisms of disease development. This information can be also helpful to improve the current diagnostic solutions for patients with idiopathic erythrocytosis.

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A novel homeostatic loop of sorcin drives paclitaxel-resistance and malignant progression via Smad4/ZEB1/miR-142-5p in human ovarian cancer

Oncogene ◽

10.1038/s41388-021-01891-6 ◽

2021 ◽

Author(s):

Jinguo Zhang ◽

Wencai Guan ◽

Xiaolin Xu ◽

Fanchen Wang ◽

Xin Li ◽

...

Keyword(s):

Ovarian Cancer ◽

Calcium Binding ◽

Molecular Mechanisms ◽

Epithelial Mesenchymal Transition ◽

Malignant Progression ◽

Bioinformatics Analyses ◽

Aberrant Expression ◽

Mesenchymal Transition ◽

E Box

AbstractThe primary chemotherapy of ovarian cancer (OC) often acquires chemoresistance. Sorcin (SRI), a soluble resistance-related calcium-binding protein, has been reported to be an oncogenic protein in cancer. However, the molecular mechanisms of SRI regulation and the role and aberrant expression of SRI in chemoresistant OC remain unclear. Here, we identified SRI as a key driver of paclitaxel (PTX)-resistance and explored its regulatory mechanism. Using transcriptome profiles, qRT-PCR, proteomics, Western blot, immunohistochemistry, and bioinformatics analyses, we found that SRI was overexpressed in PTX-resistant OC cells and the overexpression of SRI was related to the poor prognosis of patients. SRI was a key molecule required for growth, migration, and PTX-resistance in vitro and in vivo and was involved in epithelial–mesenchymal transition (EMT) and stemness. Mechanistic studies showed that miR-142-5p directly bound to the 3ʹ-UTR of SRI to suppress its expression, whereas a transcription factor zinc-finger E-box binding homeobox 1 (ZEB1) inhibited the transcription of miR-142-5p by directly binding to the E-box fragment in the miR-142 promoter region. Furthermore, ZEB1 was negatively regulated by SRI which physically interacted with Smad4 to block its translocation from the cytosol to the nucleus. Taken together, our findings unveil a novel homeostatic loop of SRI that drives the PTX-resistance and malignant progression via Smad4/ZEB1/miR-142-5p in human OC. Targeting this SRI/Smad4/ZEB1/miR-142-5p loop may reverse the PTX-resistance.

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Expression and function of Smad7 in autoimmune and inflammatory diseases

Journal of Molecular Medicine ◽

10.1007/s00109-021-02083-1 ◽

2021 ◽

Author(s):

Yiping Hu ◽

Juan He ◽

Lianhua He ◽

Bihua Xu ◽

Qingwen Wang

Keyword(s):

Posttranscriptional Regulation ◽

Molecular Mechanisms ◽

Transforming Growth Factor ◽

Inflammatory Diseases ◽

Kidney Diseases ◽

Critical Role ◽

Transforming Growth Factor Β ◽

Negative Regulator ◽

Signaling Mechanism ◽

And Function

AbstractTransforming growth factor-β (TGF-β) plays a critical role in the pathological processes of various diseases. However, the signaling mechanism of TGF-β in the pathological response remains largely unclear. In this review, we discuss advances in research of Smad7, a member of the I-Smads family and a negative regulator of TGF-β signaling, and mainly review the expression and its function in diseases. Smad7 inhibits the activation of the NF-κB and TGF-β signaling pathways and plays a pivotal role in the prevention and treatment of various diseases. Specifically, Smad7 can not only attenuate growth inhibition, fibrosis, apoptosis, inflammation, and inflammatory T cell differentiation, but also promotes epithelial cells migration or disease development. In this review, we aim to summarize the various biological functions of Smad7 in autoimmune diseases, inflammatory diseases, cancers, and kidney diseases, focusing on the molecular mechanisms of the transcriptional and posttranscriptional regulation of Smad7.

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