GUN1 regulates tetrapyrrole biosynthesis

The biogenesis of the photosynthetic apparatus in developing chloroplasts requires the assembly of proteins encoded on both nuclear and chloroplast genomes1. To co-ordinate this process there needs to be communication between these organelles, and while we have a good understanding of how the nucleus controls chloroplast development, how the chloroplast communicates with the nucleus at this time is still essentially unknown2. What we do know comes from pioneering work in which a series of genomes uncoupled (gun) mutants were identified that show elevated nuclear gene expression after chloroplast damage3. Of the six reported gun mutations, five are in tetrapyrrole biosynthesis proteins4-6 and this has led to the development of a model for chloroplast-to-nucleus retrograde signaling in which ferrochelatase 1 (FC1)-dependent heme synthesis generates a positive signal promoting expression of photosynthesis-related genes6. However, the molecular consequences of the strongest of the gun mutants, gun17, is unknown, preventing the development of a unifying hypothesis for chloroplast-to-nucleus signaling. Here, we show that GUN1 directly binds to heme and other metal-porphyrins, affects flux through the tetrapyrrole biosynthesis pathway and can increase the chelatase activity of FC1. These results raise the possibility that the signaling role of GUN1 may be manifested through changes in tetrapyrrole metabolism and supports a role for tetrapyrroles as mediators of a single biogenic chloroplast-to-nucleus retrograde signaling pathway.

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The retrograde signaling protein GUN1 regulates tetrapyrrole biosynthesis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1911251116 ◽

2019 ◽

Vol 116 (49) ◽

pp. 24900-24906 ◽

Cited By ~ 9

Author(s):

Takayuki Shimizu ◽

Sylwia M. Kacprzak ◽

Nobuyoshi Mochizuki ◽

Akira Nagatani ◽

Satoru Watanabe ◽

...

Keyword(s):

Photosynthetic Apparatus ◽

Nuclear Gene ◽

Retrograde Signaling ◽

Biosynthesis Pathway ◽

Tetrapyrrole Biosynthesis ◽

Positive Signal ◽

Nuclear Gene Expression ◽

Chloroplast Genomes ◽

Tetrapyrrole Metabolism

The biogenesis of the photosynthetic apparatus in developing seedlings requires the assembly of proteins encoded on both nuclear and chloroplast genomes. To coordinate this process there needs to be communication between these organelles, but the retrograde signals by which the chloroplast communicates with the nucleus at this time are still essentially unknown. The Arabidopsis thaliana genomes uncoupled (gun) mutants, that show elevated nuclear gene expression after chloroplast damage, have formed the basis of our understanding of retrograde signaling. Of the 6 reported gun mutations, 5 are in tetrapyrrole biosynthesis proteins and this has led to the development of a model for chloroplast-to-nucleus retrograde signaling in which ferrochelatase 1 (FC1)-dependent heme synthesis generates a positive signal promoting expression of photosynthesis-related genes. However, the molecular consequences of the strongest of the gun mutants, gun1, are poorly understood, preventing the development of a unifying hypothesis for chloroplast-to-nucleus signaling. Here, we show that GUN1 directly binds to heme and other porphyrins, reduces flux through the tetrapyrrole biosynthesis pathway to limit heme and protochlorophyllide synthesis, and can increase the chelatase activity of FC1. These results raise the possibility that the signaling role of GUN1 may be manifested through changes in tetrapyrrole metabolism, supporting a role for tetrapyrroles as mediators of a single biogenic chloroplast-to-nucleus retrograde signaling pathway.

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The Role of Tetrapyrrole- and GUN1-Dependent Signaling on Chloroplast Biogenesis

Plants ◽

10.3390/plants10020196 ◽

2021 ◽

Vol 10 (2) ◽

pp. 196

Author(s):

Takayuki Shimizu ◽

Tatsuru Masuda

Keyword(s):

Protein Import ◽

Nuclear Gene ◽

Retrograde Signaling ◽

Chloroplast Biogenesis ◽

Plastid Development ◽

Nuclear Gene Expression ◽

Coordinated Expression ◽

Plastid Protein ◽

Working Hypotheses

Chloroplast biogenesis requires the coordinated expression of the chloroplast and nuclear genomes, which is achieved by communication between the developing chloroplasts and the nucleus. Signals emitted from the plastids, so-called retrograde signals, control nuclear gene expression depending on plastid development and functionality. Genetic analysis of this pathway identified a set of mutants defective in retrograde signaling and designated genomes uncoupled (gun) mutants. Subsequent research has pointed to a significant role of tetrapyrrole biosynthesis in retrograde signaling. Meanwhile, the molecular functions of GUN1, the proposed integrator of multiple retrograde signals, have not been identified yet. However, based on the interactions of GUN1, some working hypotheses have been proposed. Interestingly, GUN1 contributes to important biological processes, including plastid protein homeostasis, through transcription, translation, and protein import. Furthermore, the interactions of GUN1 with tetrapyrroles and their biosynthetic enzymes have been revealed. This review focuses on our current understanding of the function of tetrapyrrole retrograde signaling on chloroplast biogenesis.

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Thioredoxin-dependent control balances the metabolic activities of tetrapyrrole biosynthesis

Biological Chemistry ◽

10.1515/hsz-2020-0308 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Daniel Wittmann ◽

Neha Sinha ◽

Bernhard Grimm

Keyword(s):

Environmental Changes ◽

Nuclear Gene ◽

Tetrapyrrole Biosynthesis ◽

Nuclear Gene Expression ◽

Light Levels ◽

Organ Specific ◽

Intracellular Compartments ◽

The Face ◽

Metabolic Activities ◽

The Impact

AbstractPlastids are specialized organelles found in plants, which are endowed with their own genomes, and differ in many respects from the intracellular compartments of organisms belonging to other kingdoms of life. They differentiate into diverse, plant organ-specific variants, and are perhaps the most versatile organelles known. Chloroplasts are the green plastids in the leaves and stems of plants, whose primary function is photosynthesis. In response to environmental changes, chloroplasts use several mechanisms to coordinate their photosynthetic activities with nuclear gene expression and other metabolic pathways. Here, we focus on a redox-based regulatory network composed of thioredoxins (TRX) and TRX-like proteins. Among multiple redox-controlled metabolic activities in chloroplasts, tetrapyrrole biosynthesis is particularly rich in TRX-dependent enzymes. This review summarizes the effects of plastid-localized reductants on several enzymes of this pathway, which have been shown to undergo dithiol-disulfide transitions. We describe the impact of TRX-dependent control on the activity, stability and interactions of these enzymes, and assess its contribution to the provision of adequate supplies of metabolic intermediates in the face of diurnal and more rapid and transient changes in light levels and other environmental factors.

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Overexpression of chloroplast-targeted ferrochelatase 1 results in a genomes uncoupled chloroplast-to-nucleus retrograde signalling phenotype

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2019.0401 ◽

2020 ◽

Vol 375 (1801) ◽

pp. 20190401 ◽

Cited By ~ 2

Author(s):

Mike T. Page ◽

Tania Garcia-Becerra ◽

Alison G. Smith ◽

Matthew J. Terry

Keyword(s):

Gene Expression ◽

Feedback Inhibition ◽

Nuclear Gene ◽

Signalling Pathway ◽

Chloroplast Genes ◽

Nuclear Gene Expression ◽

Retrograde Signalling ◽

Genes Encoding ◽

Retrograde Signal

Chloroplast development requires communication between the progenitor plastids and the nucleus, where most of the genes encoding chloroplast proteins reside. Retrograde signals from the chloroplast to the nucleus control the expression of many of these genes, but the signalling pathway is poorly understood. Tetrapyrroles have been strongly implicated as mediators of this signal with the current hypothesis being that haem produced by the activity of ferrochelatase 1 (FC1) is required to promote nuclear gene expression. We have tested this hypothesis by overexpressing FC1 and specifically targeting it to either chloroplasts or mitochondria, two possible locations for this enzyme. Our results show that targeting of FC1 to chloroplasts results in increased expression of the nuclear-encoded chloroplast genes GUN4 , CA1 , HEMA1 , LHCB2.1, CHLH after treatment with Norflurazon (NF) and that this increase correlates to FC1 gene expression and haem production measured by feedback inhibition of protochlorophyllide synthesis. Targeting FC1 to mitochondria did not enhance the expression of nuclear-encoded chloroplast genes after NF treatment. The overexpression of FC1 also increased nuclear gene expression in the absence of NF treatment, demonstrating that this pathway is operational in the absence of a stress treatment. Our results therefore support the hypothesis that haem synthesis is a promotive chloroplast-to-nucleus retrograde signal. However, not all FC1 overexpression lines enhanced nuclear gene expression, suggesting there is still a lot we do not understand about the role of FC1 in this signalling pathway. This article is part of the theme issue ‘Retrograde signalling from endosymbiotic organelles’.

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Plastid Signals Confer Arabidopsis Tolerance to Water Stress

Zeitschrift für Naturforschung C ◽

10.1515/znc-2011-1-207 ◽

2011 ◽

Vol 66 (1-2) ◽

pp. 47-54 ◽

Cited By ~ 3

Author(s):

Jian Cheng ◽

Chun-Xia He ◽

Zhong-Wei Zhang ◽

Fei Xu ◽

Da-Wei Zhang ◽

...

Keyword(s):

Water Stress ◽

Photosynthetic Apparatus ◽

Nuclear Gene ◽

Stress Adaptation ◽

Wild Type ◽

Oxidative Damages ◽

Nuclear Gene Expression ◽

Retrograde Signalling ◽

The Relationship ◽

Mutant Cells

Plastid-to-nucleus retrograde signalling coordinates nuclear gene expression with chloroplast function and is essential for the photoautotrophic life-style of plants. The relationship between plastid signalling and water stress response was investigated with genome uncoupled (gun) mutants, gun1, gun3, and gun5, and an abscisic acid (ABA)-responsible transcription factor mutant, abi4. The results showed that gun1, gun3, gun5, and abi4 mutants suffered from more oxidative damages than the wild-type plants under the water stress and the water stress + herbicide (norflurazon, NF) co-treatment. Superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX) activities could not be prompted in the plastidsignalling defective mutants under the stress conditions. At the same time, Lhcb expression was not repressed in the plastid-signalling defective mutants by the NF treatment or water stress. Therefore, the photosynthetic apparatus in the mutant cells could not be closed during the stresses and the excessive light caused more photodamages on the mutant leaves. The roles of GUN1, GUN3, GUN5 and ABI4 proteins in environmental stress adaptation have been discussed.

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HnRNPA2 is a novel histone acetyltransferase that mediates mitochondrial stress-induced nuclear gene expression

Cell Discovery ◽

10.1038/celldisc.2016.45 ◽

2016 ◽

Vol 2 (1) ◽

Cited By ~ 17

Author(s):

Manti Guha ◽

Satish Srinivasan ◽

Kip Guja ◽

Edison Mejia ◽

Miguel Garcia-Diaz ◽

...

Keyword(s):

Gene Expression ◽

Mitochondrial Dna ◽

Transcriptional Activation ◽

Nuclear Gene ◽

C2c12 Cells ◽

Retrograde Signaling ◽

Epigenetic Mechanism ◽

Mitochondrial Stress ◽

Nuclear Gene Expression ◽

Mitochondrial Dna Copy Number

Abstract Reduced mitochondrial DNA copy number, mitochondrial DNA mutations or disruption of electron transfer chain complexes induce mitochondria-to-nucleus retrograde signaling, which induces global change in nuclear gene expression ultimately contributing to various human pathologies including cancer. Recent studies suggest that these mitochondrial changes cause transcriptional reprogramming of nuclear genes although the mechanism of this cross talk remains unclear. Here, we provide evidence that mitochondria-to-nucleus retrograde signaling regulates chromatin acetylation and alters nuclear gene expression through the heterogeneous ribonucleoprotein A2 (hnRNAP2). These processes are reversed when mitochondrial DNA content is restored to near normal cell levels. We show that the mitochondrial stress-induced transcription coactivator hnRNAP2 acetylates Lys 8 of H4 through an intrinsic histone lysine acetyltransferase (KAT) activity with Arg 48 and Arg 50 of hnRNAP2 being essential for acetyl-CoA binding and acetyltransferase activity. H4K8 acetylation at the mitochondrial stress-responsive promoters by hnRNAP2 is essential for transcriptional activation. We found that the previously described mitochondria-to-nucleus retrograde signaling-mediated transformation of C2C12 cells caused an increased expression of genes involved in various oncogenic processes, which is retarded in hnRNAP2 silenced or hnRNAP2 KAT mutant cells. Taken together, these data show that altered gene expression by mitochondria-to-nucleus retrograde signaling involves a novel hnRNAP2-dependent epigenetic mechanism that may have a role in cancer and other pathologies.

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Light-Mediated Regulation of Leaf Senescence

International Journal of Molecular Sciences ◽

10.3390/ijms22073291 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3291

Author(s):

Yasuhito Sakuraba

Keyword(s):

Leaf Senescence ◽

Molecular Mechanisms ◽

Transcriptional Regulatory Network ◽

Current Knowledge ◽

Red Light ◽

Nuclear Gene ◽

Nuclear Gene Expression ◽

Transcriptional Regulatory ◽

Plant Life Cycle

Light is the primary regulator of various biological processes during the plant life cycle. Although plants utilize photosynthetically active radiation to generate chemical energy, they possess several photoreceptors that perceive light of specific wavelengths and then induce wavelength-specific responses. Light is also one of the key determinants of the initiation of leaf senescence, the last stage of leaf development. As the leaf photosynthetic activity decreases during the senescence phase, chloroplasts generate a variety of light-mediated retrograde signals to alter the expression of nuclear genes. On the other hand, phytochrome B (phyB)-mediated red-light signaling inhibits the initiation of leaf senescence by repressing the phytochrome interacting factor (PIF)-mediated transcriptional regulatory network involved in leaf senescence. In recent years, significant progress has been made in the field of leaf senescence to elucidate the role of light in the regulation of nuclear gene expression at the molecular level during the senescence phase. This review presents a summary of the current knowledge of the molecular mechanisms underlying light-mediated regulation of leaf senescence.

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RCD1 Coordinates Chloroplastic and Mitochondrial Electron Transfer through Interaction with ANAC Transcription Factors in Arabidopsis

10.1101/327411 ◽

2018 ◽

Cited By ~ 1

Author(s):

Alexey Shapiguzov ◽

Julia P. Vainonen ◽

Kerri Hunter ◽

Helena Tossavainen ◽

Arjun Tiwari ◽

...

Keyword(s):

Electron Transfer ◽

Transcription Factors ◽

Photosynthetic Apparatus ◽

Nuclear Gene ◽

Complex Iii ◽

Nuclear Gene Expression ◽

Mitochondrial Retrograde Signaling ◽

Thiol Redox State ◽

Thiol Redox

AbstractSignaling from chloroplasts and mitochondria, both dependent on reactive oxygen species (ROS), merge at the nuclear protein RADICAL-INDUCED CELL DEATH1 (RCD1). ROS produced in the chloroplasts affect the abundance, thiol redox state and oligomerization of RCD1. RCD1 directly interacts in vivo with ANAC013 and ANAC017 transcription factors, which are the mediators of the ROS-related mitochondrial complex III retrograde signa and suppresses activity of ANAC013 and ANAC017. Inactivation of RCD1 leads to increased expression of ANAC013 and ANAC017-regulated genes belonging to the mitochondrial dysfunction stimulon (MDS), including genes for mitochondrial alternative oxidases (AOXs). Accumulating AOXs and other MDS gene products alter electron transfer pathways in the chloroplasts, leading to diminished production of chloroplastic ROS and increased protection of photosynthetic apparatus from ROS damage. RCD1-dependent regulation affects chloroplastic and mitochondrial retrograde signaling including chloroplast signaling by 3’-phosphoadenosine 5’-phosphate (PAP). Sensitivity of RCD1 to organellar ROS provides feedback control of nuclear gene expression.

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Impact of small RNAs in retrograde signalling pathways in Arabidopsis thaliana

10.1101/798900 ◽

2019 ◽

Author(s):

Kristin Habermann ◽

Bhavika Tiwari ◽

Maria Krantz ◽

Stephan O. Adler ◽

Edda Klipp ◽

...

Keyword(s):

Gene Expression ◽

Nuclear Gene ◽

Signalling Pathways ◽

Wild Type ◽

Nuclear Gene Expression ◽

Non Coding Rna ◽

Retrograde Signalling ◽

Transcriptional Changes ◽

Non Coding Rnas

SummaryChloroplast perturbations activate retrograde signalling pathways causing dynamic changes of gene expression. Besides transcriptional control of gene expression different classes of small non-coding RNAs (sRNAs) act in gene expression control, but comprehensive analyses regarding their role in retrograde signalling is lacking. We performed sRNA profiling in response to norflurazon (NF) that provokes retrograde signals in A. thaliana wild type and the two retrograde signalling mutants gun1 and gun5. The RNA samples were also used for mRNA and long non-coding RNA (lncRNA) profiling to link altered sRNA levels to changes of their cognate target RNAs. We identified 122 sRNAs from all known sRNA classes that were responsive to NF in wild type. Strikingly, 140 and 213 sRNAs were found to be differentially regulated in both mutants indicating a retrograde control of these sRNAs. Concomitant with the changes in sRNA expression we detected about 1500 differentially expressed mRNAs in the NF treated wild type and around 900 and 1400 mRNAs that were differentially regulated in the gun1 and gun5 mutant with a high proportion (~30%) of genes encoding plastid proteins. Furthermore, around 20% of predicted miRNA targets code for plastid localised proteins. The analyses of sRNA-target pairs identified pairs with an anticorrelated expression as well pairs showing other expressional relations pointing to a role of sRNAs in balancing transcriptional changes upon retrograde signals. Based on the comprehensive changes in sRNA expression we assume a considerable impact of sRNAs in retrograde-dependent transcriptional changes to adjust plastidic and nuclear gene expression.Significance statementPerturbations of plastid functions trigger retrograde signalling to adjust plastidic and nuclear gene expression, however, the role of small non-coding RNAs acting as regulators in these pathways is not well understood. We analysed small non-coding RNA expression in response to retrograde signals in A. thaliana wild type and two retrograde signalling mutants and identified members of all known small non-coding RNA classes pointing to a functional role of these RNA classes in retrograde pathways.

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Dual-targeted transcription factors are required for optimal photosynthesis and stress responses in Arabidopsis thaliana

10.1101/793968 ◽

2019 ◽

Cited By ~ 1

Author(s):

Piotr Gawroński ◽

Paweł Burdiak ◽

Lars B. Scharff ◽

Jakub Mielecki ◽

Magdalena Zaborowska ◽

...

Keyword(s):

Transcription Factors ◽

Stress Responses ◽

Environmental Changes ◽

Cell Function ◽

Nuclear Gene ◽

Transit Peptide ◽

Protein Translation ◽

Retrograde Signaling ◽

Nuclear Gene Expression ◽

Chloroplast Translation

SummaryChloroplast to nucleus retrograde signaling is essential for cell function, acclimation to fluctuating environmental conditions, plant growth and development. The vast majority of chloroplast proteins are nuclear-encoded and must be imported into the organelle after synthesis in the cytoplasm. This import is essential for the development of fully functional chloroplasts. On the other hand, functional chloroplasts act as sensors of environmental changes and can trigger acclimatory responses that influence nuclear gene expression. Signaling via mobile transcription factors (TFs) has been recently recognized as a way of communication between organelles and the nucleus. In this study, we performed a targeted reverse genetic screen to identify novel dual-localized TFs involved in chloroplast retrograde signaling during stress responses. We found that CHLOROPLAST IMPORT APPARATUS 2 (CIA2), a TF with putative plastid transit peptide can be detected in chloroplasts and the nucleus. Further, we found that CIA2, along with its homolog CIA2-like (CIL) act in an unequally redundant manner and are involved in the regulation of Arabidopsis responses to UV-AB, high light, and heat shock. Finally, our results suggest that both CIA2 and CIL are crucial for chloroplast translation. Our results contribute to a deeper understanding of signaling events in the chloroplast-nucleus cross-talk.SignificanceWe found that a transcription factor CIA2 can be located in chloroplasts and nucleus. CIA2 and is close homolog CIL are involved in protein translation and abiotic stress responses, and we suggest that they play an essential role in retrograde signaling between these organelles.

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