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6. Pro-vegetarian dietary patterns and essential and heavy metal exposure in children of 4-5-years from the INfancia y medio Ambiente cohort (INMA)

Author

Oncina-Cánovas, Alejandro, Vioque, Jesús, Riutort-Mayol, Gabriel, Soler-Blasco, Raquel, Irizar, Amaia, Barroeta, Ziortza, Fernández-Somoano, Ana, Tardón, Adonina, Vrijheid, Martine, Guxens, Mònica, Carey, Manus, Meharg, Caroline, Ralphs, Kathryn, McCreanor, Coalain, Meharg, Andrew, and Signes-Pastor, Antonio J.

Published
2024
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8. Global Geographical Variation in Elemental and Arsenic Species Concentration in Paddy Rice Grain Identifies a Close Association of Essential Elements Copper, Selenium and Molybdenum with Cadmium

Author

Meharg, Andrew A., Meharg, Caroline, Carey, Manus, Williams, Paul, Shi, Zhengyu, Campbell, Katrina, Elliott, Christopher, Marwa, Ernest, Jiujin, Xiao, Farias, Júlia Gomes, Nicoloso, Fernando Teixeira, De Silva, P. Mangala C. S., Lu, Ying, Green, Andy J., Moreno-Jiménez, Eduardo, Carbonell-Barrachina, Ángel Antonio, Sommella, Alessia, Pigna, Massimo, Brabet, Catherine, Montet, Didier, Hossain, Mahmud, and Islam, M. Rafiqul

Published
2022
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9. Enterobacter Species

Author

Skinnader, Oisin, primary, Nguyen, Scott, additional, Marshall, Helina, additional, Meharg, Caroline, additional, and Fanning, Séamus, additional

Published
2022
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12. Global Sourcing of Low-Inorganic Arsenic Rice Grain

Author

Carey, Manus, Meharg, Caroline, Williams, Paul, Marwa, Ernest, Jiujin, Xiao, Farias, Júlia Gomes, De Silva, P. Mangala C. S., Signes-Pastor, Antonio, Lu, Ying, Nicoloso, Fernando Teixeira, Savage, Laurie, Campbell, Katrina, Elliott, Christopher, Adomako, Eureka, Green, Andy J., Moreno-Jiménez, Eduardo, Carbonell-Barrachina, Ángel Antonio, Triwardhani, Eridha Ayu, Pandiangan, Febbyandi Isanda, Haris, Parvez I., Lawgali, Youssef F., Sommella, Alessia, Pigna, Massimo, Brabet, Catherine, Montet, Didier, Njira, Keston, Watts, Michael J., and Meharg, Andrew A.

Published
2020
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13. Rice Grain Cadmium Concentrations in the Global Supply-Chain

Author

Shi, Zhengyu, Carey, Manus, Meharg, Caroline, Williams, Paul N., Signes-Pastor, Antonio J., Triwardhani, Eridha Ayu, Pandiangan, Febbyandi Isnanda, Campbell, Katrina, Elliott, Christopher, Marwa, Ernest M., Jiujin, Xiao, Farias, Júlia Gomes, Nicoloso, Fernando Teixeira, De Silva, P. Mangala C. S., Lu, Ying, Norton, Gareth, Adomako, Eureka, Green, Andy J., Moreno-Jiménez, Eduardo, Zhu, Yongguan, Carbonell-Barrachina, Ángel Antonio, Haris, Parvez I., Lawgali, Youssef F., Sommella, Alessia, Pigna, Massimo, Brabet, Catherine, Montet, Didier, Njira, Keston, Watts, Michael J., Hossain, Mahmud, Islam, M. Rafiqul, Tapia, Yasna, Oporto, Carla, and Meharg, Andrew A.

Published
2020
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17. Global geographical variation in elemental and arsenic species concentration in paddy rice grain identifies a close association of essential elements copper, selenium and molybdenum with cadmium

Author

Meharg, Andrew A., Meharg, Caroline, Carey, Manus, Williams, Paul N., Shi, Zhengyu, Campbell, Katrina, Elliott, Christopher T., Marwa, Enerst M., Jiujin, Xiao, Gomes Farias, Júlia, Teixeira Nicoloso, Fernando, De Silva, P. Mangala C. S., Lu, Ying, Green, Andy, Moreno-Jiménez, Eduardo, Carbonell-Barrachina, Ángel Antonio, Sommella, Alessia, Pigna, Massimo, Brabet, Catherine, Montet, Didier, Hossain, Mahmud, Islam, M. Rafiqul, Meharg, Andrew A., Meharg, Caroline, Carey, Manus, Williams, Paul N., Shi, Zhengyu, Campbell, Katrina, Elliott, Christopher T., Marwa, Enerst M., Jiujin, Xiao, Gomes Farias, Júlia, Teixeira Nicoloso, Fernando, De Silva, P. Mangala C. S., Lu, Ying, Green, Andy, Moreno-Jiménez, Eduardo, Carbonell-Barrachina, Ángel Antonio, Sommella, Alessia, Pigna, Massimo, Brabet, Catherine, Montet, Didier, Hossain, Mahmud, and Islam, M. Rafiqul

Abstract

Despite the centrality of staple grains for human well-being, both as a source of nutrients and of toxic ions, there is little understanding of where and how elements vary, and if there are particular elements that correlate. Here, for shop bought polished (white) rice, we comprehensively characterized trace (arsenic species, cadmium, copper, iron, manganese, molybdenum, rubidium and zinc) and macro-nutrients (calcium, chlorine, potassium, phosphorus and sulphur) for grain purchased in 18 countries, across four continents, a total of 1045 samples. This was to investigate if there were any major differences between geographic location and elemental content, and to observe if there were any patterns in elemental distribution. Greatest variation in the median was observed for the non-essential rubidium (15-fold) and arsenic species (fivefold). Rubidium was the highest in the Americas, lowest in Europe, while inorganic arsenic (iAs) and dimethylarsonic acid (DMA) were low for Africa and high in the South American and European continents. The highest concentrations of cadmium were found in Asian samples, and lowest in South America, with variation within these regions. At the extremes of individual counties, China had fivefold higher concentrations than the global median, while Tanzania was fourfold lower than this value. Calcium, potassium, molybdenum and phosphorus were the highest in European and lowest in African grain, though the fold-differences were relatively low, ~ 0.2, while iron was the highest in African grain and lowest in European, Asian and South American grain, with a ~ twofold difference. Selenium was also higher in Africa versus other regions, and copper, manganese and zinc were the highest in American grain. Factor analysis showed that copper, cadmium, molybdenum, rubidium and selenium were strongly associated together, and these element's factor loadings were diametrically opposed to less tightly associated calcium, chlorine, manganese, potassium, pho

Published
2023

18. Rice Grain Cadmium Concentrations in the Global Supply-Chain

Author

Shi, Zhengyu, Carey, Manus, Meharg, Caroline, Williams, Paul N., Signes-Pastor, Antonio J., Triwardhani, Eridha Ayu, Pandiangan, Febbyandi Isnanda, Campbell, Katrina, Elliott, Christopher, Marwa, Ernest M., Jiujin, Xiao, Farias, Júlia Gomes, Nicoloso, Fernando Teixeira, De Silva, P. Mangala C. S., Lu, Ying, Norton, Gareth, Adomako, Eureka, Green, Andy J., Moreno-Jiménez, Eduardo, Zhu, Yongguan, Carbonell-Barrachina, Ángel Antonio, Haris, Parvez I., Lawgali, Youssef F., Sommella, Alessia, Pigna, Massimo, Brabet, Catherine, Montet, Didier, Njira, Keston, Watts, Michael J., Hossain, Mahmud, Islam, M. Rafiqul, Tapia, Yasna, Oporto, Carla, and Meharg, Andrew A.

Abstract

One of cadmium’s major exposure routes to humans is through rice consumption. The concentrations of cadmium in the global polished (white), market rice supply-chain were assessed in 2270 samples, purchased from retailers across 32 countries, encompassing 6 continents. It was found on a global basis that East Africa had the lowest cadmium with a median for both Malawi and Tanzania at 4.9 μg/kg, an order of magnitude lower than the highest country, China with a median at 69.3 μg/kg. The Americas were typically low in cadmium, but the Indian sub-continent was universally elevated. In particular certain regions of Bangladesh had high cadmium, that when combined with the high daily consumption rate of rice of that country, leads to high cadmium exposures. Concentrations of cadmium were compared to the European Standard for polished rice of 200 μg/kg and 5% of the global supply-chain exceeded this threshold. For the stricter standard of 40 μg/kg for processed infant foods, for which rice can comprise up to 100% by composition (such as rice porridges, puffed rice cereal and cakes), 25% of rice would not be suitable for making pure rice baby foods. Given that rice is also elevated in inorganic arsenic, the only region of the world where both inorganic arsenic and cadmium were low in grain was East Africa.

Published
2024
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19. Global Sourcing of Low-Inorganic Arsenic Rice Grain

Author

Carey, Manus, Meharg, Caroline, Williams, Paul, Marwa, Ernest, Jiujin, Xiao, Farias, Júlia Gomes, De Silva, P. Mangala C. S., Signes-Pastor, Antonio, Lu, Ying, Nicoloso, Fernando Teixeira, Savage, Laurie, Campbell, Katrina, Elliott, Christopher, Adomako, Eureka, Green, Andy J., Moreno-Jiménez, Eduardo, Carbonell-Barrachina, Ángel Antonio, Triwardhani, Eridha Ayu, Pandiangan, Febbyandi Isanda, Haris, Parvez I., Lawgali, Youssef F., Sommella, Alessia, Pigna, Massimo, Brabet, Catherine, Montet, Didier, Njira, Keston, Watts, Michael J., and Meharg, Andrew A.

Abstract

Arsenic in rice grain is dominated by two species: the carcinogen inorganic arsenic (the sum of arsenate and arsenite) and dimethylarsinic acid (DMA). Rice is the dominant source of inorganic arsenic into the human diet. As such, there is a need to identify sources of low-inorganic arsenic rice globally. Here we surveyed polished (white) rice across representative regions of rice production globally for arsenic speciation. In total 1180 samples were analysed from 29 distinct sampling zones, across 6 continents. For inorganic arsenic the global x~was 66 μg/kg, and for DMA this figure was 21 μg/kg. DMA was more variable, ranging from < 2 to 690 μg/kg, while inorganic arsenic ranged from < 2 to 399 μg/kg. It was found that inorganic arsenic dominated when grain sum of species was < 100 μg/kg, with DMA dominating at higher concentrations. There was considerable regional variance in grain arsenic speciation, particularly in DMA where temperate production regions had higher concentrations. Inorganic arsenic concentrations were relatively consistent across temperate, subtropical and northern hemisphere tropical regions. It was only in southern hemisphere tropical regions, in the eastern hemisphere that low-grain inorganic arsenic is found, namely East Africa (x~< 10 μg/kg) and the Southern Indonesian islands (x~< 20 μg/kg). Southern hemisphere South American rice was universally high in inorganic arsenic, the reason for which needs further exploration.

Published
2024
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20. Recycled Household Ash in Rice Paddies of Bangladesh for Sustainable Production of Rice Without Altering Grain Arsenic and Cadmium

Author

Gupta, Yogesh, primary, Hossain, Mahmud, additional, Islam, M. Rafiqul, additional, Talukder, Md. Moyeed Hasan, additional, Khokon, Md. Atiqur Rahman, additional, Uddin, Mohammad Mahir, additional, Kabir, Humayun, additional, Carey, Manus, additional, Ralphs, Kathryn, additional, de Moraes, Natalia Valadares, additional, Meharg, Andrew A., additional, and Meharg, Caroline, additional

Published
2023
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21. Correction to: Global Sourcing of Low-Inorganic Arsenic Rice Grain

Author

Carey, Manus, Meharg, Caroline, Williams, Paul, Marwa, Ernest, Jiujin, Xiao, Farias, Júlia Gomes, De Silva, P. Mangala C. S., Signes-Pastor, Antonio, Lu, Ying, Nicoloso, Fernando Teixeira, Savage, Laurie, Campbell, Katrina, Elliott, Christopher, Adomako, Eureka, Green, Andy J., Moreno-Jiménez, Eduardo, Carbonell-Barrachina, Ángel Antonio, Triwardhani, Eridha Ayu, Pandiangan, Febbyandi Isanda, Haris, Parvez I., Lawgali, Youssef F., Sommella, Alessia, Pigna, Massimo, Brabet, Catherine, Montet, Didier, Njira, Keston, Watts, Michael J., and Meharg, Andrew A.

Published
2020
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27. Global geographical variation elemental and arsenic species concentration in paddy rice grain identifies a close association of essential elements copper, selenium and molybdenum with cadmium.

Author

Meharg, Prof. Andrew, primary, Meharg, Caroline, additional, Carey, Manus, additional, Williams, Paul, additional, Shi, Zhengyu, additional, Campbell, Katrina, additional, Elliott, Christopher, additional, Marwa, Ernest, additional, Jiujin, Xiao, additional, Farias, Júlia Gomes, additional, Nicoloso, Fernando Teixeira, additional, De Silva, P. Mangala C.S., additional, Lu, Ying, additional, Green, Andy J., additional, Moreno-Jiménez, Eduardo, additional, Carbonell-Barrachina, Ángel Antonio, additional, Sommella, Alessia, additional, Pigna, Massimo, additional, Brabet, Catherine, additional, Montet, Didier, additional, Hossain, Mahmud, additional, and Islam, M. Rafiqul, additional

Published
2022
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30. The Integrated RNA Landscape of Renal Preconditioning against Ischemia-Reperfusion Injury

Author

Johnsen, Marc, Kubacki, Torsten, Yeroslaviz, Assa, Spaeth, Martin Richard, Moersdorf, Jannis, Gobel, Heike, Bohl, Katrin, Ignarski, Michael, Meharg, Caroline, Habermann, Bianca, Altmueller, Janine, Beyer, Andreas, Benzing, Thomas, Schermer, Bernhard, Burst, Volker, Mueller, Roman-Ulrich, Johnsen, Marc, Kubacki, Torsten, Yeroslaviz, Assa, Spaeth, Martin Richard, Moersdorf, Jannis, Gobel, Heike, Bohl, Katrin, Ignarski, Michael, Meharg, Caroline, Habermann, Bianca, Altmueller, Janine, Beyer, Andreas, Benzing, Thomas, Schermer, Bernhard, Burst, Volker, and Mueller, Roman-Ulrich

Abstract

Background Although AKI lacks effective therapeutic approaches, preventive strategies using preconditioning protocols, including caloric restriction and hypoxic preconditioning, have been shown to prevent injury in animal models. A better understanding of the molecular mechanisms that underlie the enhanced resistance to AKI conferred by such approaches is needed to facilitate clinical use. We hypothesized that these preconditioning strategies use similar pathways to augment cellular stress resistance. Methods To identify genes and pathways shared by caloric restriction and hypoxic preconditioning, we used RNA-sequencing transcriptome profiling to compare the transcriptional response with both modes of preconditioning in mice before and after renal ischemia-reperfusion injury. Results The gene expression signatures induced by both preconditioning strategies involve distinct common genes and pathways that overlap significantly with the transcriptional changes observed after ischemia-reperfusion injury. These changes primarily affect oxidation-reduction processes and have a major effect on mitochondrial processes. We found that 16 of the genes differentially regulated by both modes of preconditioning were strongly correlated with clinical outcome; most of these genes had not previously been directly linked to AKI. Conclusions This comparative analysis of the gene expression signatures in preconditioning strategies shows overlapping patterns in caloric restriction and hypoxic preconditioning, pointing toward common molecular mechanisms. Our analysis identified a limited set of target genes not previously known to be associated with AKI; further study of their potential to provide the basis for novel preventive strategies is warranted. To allow for optimal interactive usability of the data by the kidney research community, we provide an online interface for user-defined interrogation of the gene expression datasets (http://shiny.cecad.uni-koeln.de:3838/IRaP/).

Published
2020

32. The Integrated RNA Landscape of Renal Preconditioning against Ischemia-Reperfusion Injury

Author

Johnsen, Marc, primary, Kubacki, Torsten, additional, Yeroslaviz, Assa, additional, Späth, Martin Richard, additional, Mörsdorf, Jannis, additional, Göbel, Heike, additional, Bohl, Katrin, additional, Ignarski, Michael, additional, Meharg, Caroline, additional, Habermann, Bianca, additional, Altmüller, Janine, additional, Beyer, Andreas, additional, Benzing, Thomas, additional, Schermer, Bernhard, additional, Burst, Volker, additional, and Müller, Roman-Ulrich, additional

Published
2020
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33. Inhibiting translation elongation can aid genome duplication in Escherichia coli

Author

Myka, Kamila Katarzyna, Hawkins, Michelle, Syeda, Aisha H, Gupta, Milind K., Meharg, Caroline, Dillingham, Mark S., Savery, Nigel J., Lloyd, Robert G., and McGlynn, Peter

Subjects
DNA Replication, Peptide Chain Elongation, Translational, dna, Genome Integrity, Repair and Replication, dna-directed rna polymerase, antibiotics, transfer rna, ribosomes, Suppression, Genetic, Escherichia coli, rna, proline, genes, genome, guanosine tetraphosphate, chromosomal duplication, molecule, RNA, Transfer, Asp, translating, Escherichia coli Proteins, DNA Helicases, binding (molecular function), Mutation, gene expression, Transfer RNA Aminoacylation, mutation, escherichia coli, signal transduction, amino acyl-trna synthetases, complex, Genome, Bacterial
Abstract

Conflicts between replication and transcription challenge chromosome duplication. Escherichia coli replisome movement along transcribed DNA is promoted by Rep and UvrD accessory helicases with Δrep ΔuvrD cells being inviable under rapid growth conditions. We have discovered that mutations in a tRNA gene, aspT, in an aminoacyl tRNA synthetase, AspRS, and in a translation factor needed for efficient proline-proline bond formation, EF-P, suppress Δrep ΔuvrD lethality. Thus replication-transcription conflicts can be alleviated by the partial sacrifice of a mechanism that reduces replicative barriers, namely translating ribosomes that reduce RNA polymerase backtracking. Suppression depends on RelA-directed synthesis of (p)ppGpp, a signalling molecule that reduces replication-transcription conflicts, with RelA activation requiring ribosomal pausing. Levels of (p)ppGpp in these suppressors also correlate inversely with the need for Rho activity, an RNA translocase that can bind to emerging transcripts and displace transcription complexes. These data illustrate the fine balance between different mechanisms in facilitating gene expression and genome duplication and demonstrate that accessory helicases are a major determinant of this balance. This balance is also critical for other aspects of bacterial survival: the mutations identified here increase persistence indicating that similar mutations could arise in naturally occurring bacterial populations facing antibiotic challenge.

Published
2016

34. Resolving candidate genes of mouse skeletal muscle QTL via RNA-Seq and expression network analyses

Author

Lionikas Arimantas, Meharg Caroline, Derry Jonathan MJ, Ratkevicius Aivaras, Carroll Andrew M, Vandenbergh David J, and Blizard David A

Subjects
Functional genomics, QTL, Skeletal muscle, Gene expression, Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background We have recently identified a number of Quantitative Trait Loci (QTL) contributing to the 2-fold muscle weight difference between the LG/J and SM/J mouse strains and refined their confidence intervals. To facilitate nomination of the candidate genes responsible for these differences we examined the transcriptome of the tibialis anterior (TA) muscle of each strain by RNA-Seq. Results 13,726 genes were expressed in mouse skeletal muscle. Intersection of a set of 1061 differentially expressed transcripts with a mouse muscle Bayesian Network identified a coherent set of differentially expressed genes that we term the LG/J and SM/J Regulatory Network (LSRN). The integration of the QTL, transcriptome and the network analyses identified eight key drivers of the LSRN (Kdr, Plbd1, Mgp, Fah, Prss23, 2310014F06Rik, Grtp1, Stk10) residing within five QTL regions, which were either polymorphic or differentially expressed between the two strains and are strong candidates for quantitative trait genes (QTGs) underlying muscle mass. The insight gained from network analysis including the ability to make testable predictions is illustrated by annotating the LSRN with knowledge-based signatures and showing that the SM/J state of the network corresponds to a more oxidative state. We validated this prediction by NADH tetrazolium reductase staining in the TA muscle revealing higher oxidative potential of the SM/J compared to the LG/J strain (p Conclusion Thus, integration of fine resolution QTL mapping, RNA-Seq transcriptome information and mouse muscle Bayesian Network analysis provides a novel and unbiased strategy for nomination of muscle QTGs.

Published
2012
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36. Additional file 14: of Microbiome and ecotypic adaption of Holcus lanatus (L.) to extremes of its soil pH range, investigated through transcriptome sequencing

Author

Young, Ellen, Carey, Manus, Meharg, Andrew, and Meharg, Caroline

Abstract

Significantly expressed and KOG annotated Glomeromycotina transcripts in root and shoot in each soil. The number of significantly expressed and KOG annotated Glomeromycotina transcripts (All) is defined as the number of transcripts that obtained ≥5 aligned reads in at least 3 samples from each of the following treatments: root acid bog soil (RA), root lime soil (RL), shoot acid bog soil (SA) and shoot lime soil (SL). Significant ecotype effects (absolute log2FC ≥ 1 or ≤ − 1, FDR

Published
2018
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39. Global Sourcing of Low-Inorganic Arsenic Rice Grain

Author

Carey, Manus, primary, Meharg, Caroline, additional, Williams, Paul, additional, Marwa, Ernest, additional, Jiujin, Xiao, additional, Farias, Júlia Gomes, additional, De Silva, P. Mangala C. S., additional, Signes-Pastor, Antonio, additional, Lu, Ying, additional, Nicoloso, Fernando Teixeira, additional, Savage, Laurie, additional, Campbell, Katrina, additional, Elliott, Christopher, additional, Adomako, Eureka, additional, Green, Andy J., additional, Moreno-Jiménez, Eduardo, additional, Carbonell-Barrachina, Ángel Antonio, additional, Triwardhani, Eridha Ayu, additional, Pandiangan, Febbyandi Isanda, additional, Haris, Parvez I., additional, Lawgali, Youssef F., additional, Sommella, Alessia, additional, Pigna, Massimo, additional, Brabet, Catherine, additional, Montet, Didier, additional, Njira, Keston, additional, Watts, Michael J., additional, and Meharg, Andrew A., additional

Published
2019
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42. The developmental and genetic basis of ‘clubfoot’ in the peroneal muscular atrophy mutant mouse

Author

Collinson, J. Martin, primary, Lindström, Nils O., additional, Neves, Carlos, additional, Wallace, Karen, additional, Meharg, Caroline, additional, Charles, Rebecca H., additional, Ross, Zoe K., additional, Fraser, Amy M., additional, Mbogo, Ivan, additional, Oras, Kadri, additional, Nakamoto, Masaru, additional, Barker, Simon, additional, Duce, Suzanne, additional, Miedzybrodzka, Zosia, additional, and Vargesson, Neil, additional

Published
2018
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44. Correction to: Global Sourcing of Low-Inorganic Arsenic Rice Grain

Author

Carey, Manus, Meharg, Caroline, Williams, Paul, Marwa, Ernest, Jiujin, Xiao, Farias, Júlia Gomes, De Silva, P. Mangala C. S., Signes-Pastor, Antonio, Lu, Ying, Nicoloso, Fernando Teixeira, Savage, Laurie, Campbell, Katrina, Elliott, Christopher, Adomako, Eureka, Green, Andy J., Moreno-Jiménez, Eduardo, Carbonell-Barrachina, Ángel Antonio, Triwardhani, Eridha Ayu, Pandiangan, Febbyandi Isanda, Haris, Parvez I., Lawgali, Youssef F., Sommella, Alessia, Pigna, Massimo, Brabet, Catherine, Montet, Didier, Njira, Keston, Watts, Michael J., and Meharg, Andrew A.

Abstract

The last column in Table 1, “As air conc.” is not used in the text and was included by mistake.

Published
2024
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45. NSUN4 Is a Dual Function Mitochondrial Protein Required for Both Methylation of 12S rRNA and Coordination of Mitoribosomal Assembly

Author

Metodiev, Metodi Dimitrov, Spåhr, Henrik, Loguercio Polosa, Paola, Meharg, Caroline, Becker, Christian, Altmueller, Janine, Habermann, Bianca, Larsson, Nils-Göran, and Ruzzenente, Benedetta

Subjects
lcsh:QH426-470, Proteins, Gene Expression, Methyltransferases, DNA Methylation, Biochemistry, Mitochondria, Nucleic acids, Mitochondrial Proteins, lcsh:Genetics, Mice, RNA processing, RNA, Ribosomal, Genetics, RNA, Animals, Protein Translation, Carrier Proteins, Biology, Ribosomes, Research Article, Protein Binding, Transcription Factors
Abstract

Biogenesis of mammalian mitochondrial ribosomes requires a concerted maturation of both the small (SSU) and large subunit (LSU). We demonstrate here that the m5C methyltransferase NSUN4, which forms a complex with MTERF4, is essential in mitochondrial ribosomal biogenesis as mitochondrial translation is abolished in conditional Nsun4 mouse knockouts. Deep sequencing of bisulfite-treated RNA shows that NSUN4 methylates cytosine 911 in 12S rRNA (m5C911) of the SSU. Surprisingly, NSUN4 does not need MTERF4 to generate this modification. Instead, the NSUN4/MTERF4 complex is required to assemble the SSU and LSU to form a monosome. NSUN4 is thus a dual function protein, which on the one hand is needed for 12S rRNA methylation and, on the other hand interacts with MTERF4 to facilitate monosome assembly. The presented data suggest that NSUN4 has a key role in controlling a final step in ribosome biogenesis to ensure that only the mature SSU and LSU are assembled., Author Summary Mitochondria perform a number of essential functions in the cell, including synthesis of ATP via the oxidative phosphorylation (OXPHOS) system. Normal mitochondrial function requires coordinated expression of two genomes: mitochondria's own genome (mtDNA), which encodes 13 respiratory chain subunits with essential structural and functional roles for the OXPHOS system, and the nuclear genome encoding the remaining ∼80 subunits. The mtDNA-encoded polypeptides are synthesized on mitochondrial ribosomes (mitoribosomes) located in the mitochondrial matrix. Biogenesis, maintenance and regulation of the complex mitochondrial translation apparatus are poorly understood despite its fundamental importance for cellular energy homeostasis. Here, we show that inactivation of the Nsun4 gene, encoding a mitochondrial m5C-methyltransferase, causes embryonic lethality, whereas tissue-specific disruption of Nsun4 in the heart causes cardiomyopathy with mitochondrial dysfunction. By performing sequencing of bisulfite-treated RNA we report that NSUN4 methylates C911 in 12S rRNA of the small ribosomal subunit. Surprisingly, NSUN4 can on its own perform this rRNA modification, whereas interaction with its partner protein MTERF4 is required for assembly of functional ribosomes. NSUN4 thus has dual roles in ribosome maturation and performs an important final quality control step to ensure that only mature mitoribosomal subunits are assembled into functional ribosomes.

Published
2014

49. Inhibition of Microbial Methylation via arsMin the Rhizosphere: Arsenic Speciation in the Soil to Plant Continuum

Author

Afroz, Hasina, Su, Shiming, Carey, Manus, Meharg, Andy A., and Meharg, Caroline

Abstract

The interplay between rice roots and manuring with respect to arsenic speciation, subsequent assimilation into roots, and translocation to shoots in paddy soil was investigated, alongside bacterial diversity characterization. Planting increased soil Eh and decreased soil solution arsenic species: inorganic arsenic, monomethylarsonic acid, trimethylarsenic oxide, and dimethylarsinic acid. Presence of plant roots increased the copy number of Clostridiumand Tumebacillus16S rRNA as well as Streptomycesarsenic methylating gene (arsM), but decreased Acidobacteria_GP116S rRNA and Rhodopseudomonas. palustris BisB5 arsM. Sum of arsenic species decreased under root influence due to the interplay of inorganic arsenic mobilization in bulk soil under anaerobic and immobilization under oxygenated rhizospheric conditions. Manuring increased all soil solution arsenic species (>90%), shoot total arsenic (60%), copy number of Geobacter16S rRNA, and R. palustris TIE-1 arsM, indicative of a shift towards microbes with iron reduction and oxidation as well as arsenic methylation capabilities.

Published
2019
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