Melatonin Mitigates Cd-Induced Growth Repression and RNA m<sup>6</sup>A Hypermethylation by Triggering MMR-Mediated DNA Damage Response
Melatonin (MT) has been found to mitigate cadmium (Cd) toxicity with negligible environmental risks. It remains poorly understood as to how MT mitigates Cd-induced growth repression and regulates RNA m<sup>6</sup>A methylation. We aimed to elucidate the effect of MT on growth repression...
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2025-05-01
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| author | Zihan Tang Hetong Wang Xianpeng Wang Richard A. Ludlow Zhouli Liu Min Zhang Qijiang Cao Wan Liu Qiang Zhao |
| author_facet | Zihan Tang Hetong Wang Xianpeng Wang Richard A. Ludlow Zhouli Liu Min Zhang Qijiang Cao Wan Liu Qiang Zhao |
| author_sort | Zihan Tang |
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| description | Melatonin (MT) has been found to mitigate cadmium (Cd) toxicity with negligible environmental risks. It remains poorly understood as to how MT mitigates Cd-induced growth repression and regulates RNA m<sup>6</sup>A methylation. We aimed to elucidate the effect of MT on growth repression and RNA m<sup>6</sup>A methylation in Arabidopsis (<i>Arabidopsis thaliana</i>) exposed to Cd stress. MT mitigated, on average, 13.96% and 8.42% of growth repression resulting from Cd and mismatch repair (MMR) deficiency. The ameliorative effect on Cd stress was reduced by 70.56% and 34.23% in <i>msh2</i> and <i>msh6</i> mutants, respectively. With distinct dose–effect relationships, m<sup>6</sup>A hypermethylation responded to Cd stress rather than Cu stress, which was further elevated in MMR-deficient seedlings. MT reduced m<sup>6</sup>A levels by 22.98% even without stress induction, whereas the depressed m<sup>6</sup>A levels in MMR-deficient seedlings, greatly exceeding those in the WT. The “writer” and “eraser” gene expression responsible for m<sup>6</sup>A methylation was reduced with the concentration of stresses due to MT, but <i>VIR</i> and <i>ALKBH9B</i> no longer responded to Cd stress in <i>msh2</i> and <i>msh6</i>. Despite the remarkable repression, MMR gene expression was regularly promoted by MT under Cd and Cu stress. Our study provides novel insights into the molecular mechanisms underlying the restorative effects of MT on growth repression and m<sup>6</sup>A methylation regulation, which shed light on Cd phytoremediation. |
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| publishDate | 2025-05-01 |
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| spelling | doaj-art-40f608fecba94adcad0f8a366ab7ae192025-08-20T03:52:57ZengMDPI AGPlants2223-77472025-05-01149139810.3390/plants14091398Melatonin Mitigates Cd-Induced Growth Repression and RNA m<sup>6</sup>A Hypermethylation by Triggering MMR-Mediated DNA Damage ResponseZihan Tang0Hetong Wang1Xianpeng Wang2Richard A. Ludlow3Zhouli Liu4Min Zhang5Qijiang Cao6Wan Liu7Qiang Zhao8Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, College of Life Science and Bioengineering, Shenyang University, Shenyang 110044, ChinaLiaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, College of Life Science and Bioengineering, Shenyang University, Shenyang 110044, ChinaLiaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, College of Life Science and Bioengineering, Shenyang University, Shenyang 110044, ChinaSchool of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff CF10 3AX, UKLiaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, College of Life Science and Bioengineering, Shenyang University, Shenyang 110044, ChinaLiaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, College of Life Science and Bioengineering, Shenyang University, Shenyang 110044, ChinaLiaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, College of Life Science and Bioengineering, Shenyang University, Shenyang 110044, ChinaCollege of Agriculture and Biological Sciences, Dehong Normal University, Mangshi 678400, ChinaCollege of Agriculture, Heilongjiang Bayi Agricultural University, Daqing 163000, ChinaMelatonin (MT) has been found to mitigate cadmium (Cd) toxicity with negligible environmental risks. It remains poorly understood as to how MT mitigates Cd-induced growth repression and regulates RNA m<sup>6</sup>A methylation. We aimed to elucidate the effect of MT on growth repression and RNA m<sup>6</sup>A methylation in Arabidopsis (<i>Arabidopsis thaliana</i>) exposed to Cd stress. MT mitigated, on average, 13.96% and 8.42% of growth repression resulting from Cd and mismatch repair (MMR) deficiency. The ameliorative effect on Cd stress was reduced by 70.56% and 34.23% in <i>msh2</i> and <i>msh6</i> mutants, respectively. With distinct dose–effect relationships, m<sup>6</sup>A hypermethylation responded to Cd stress rather than Cu stress, which was further elevated in MMR-deficient seedlings. MT reduced m<sup>6</sup>A levels by 22.98% even without stress induction, whereas the depressed m<sup>6</sup>A levels in MMR-deficient seedlings, greatly exceeding those in the WT. The “writer” and “eraser” gene expression responsible for m<sup>6</sup>A methylation was reduced with the concentration of stresses due to MT, but <i>VIR</i> and <i>ALKBH9B</i> no longer responded to Cd stress in <i>msh2</i> and <i>msh6</i>. Despite the remarkable repression, MMR gene expression was regularly promoted by MT under Cd and Cu stress. Our study provides novel insights into the molecular mechanisms underlying the restorative effects of MT on growth repression and m<sup>6</sup>A methylation regulation, which shed light on Cd phytoremediation.https://www.mdpi.com/2223-7747/14/9/1398Cd toxicologyRNA m<sup>6</sup>A methylationDNA repaircell cycleArabidopsis |
| spellingShingle | Zihan Tang Hetong Wang Xianpeng Wang Richard A. Ludlow Zhouli Liu Min Zhang Qijiang Cao Wan Liu Qiang Zhao Melatonin Mitigates Cd-Induced Growth Repression and RNA m<sup>6</sup>A Hypermethylation by Triggering MMR-Mediated DNA Damage Response Plants Cd toxicology RNA m<sup>6</sup>A methylation DNA repair cell cycle Arabidopsis |
| title | Melatonin Mitigates Cd-Induced Growth Repression and RNA m<sup>6</sup>A Hypermethylation by Triggering MMR-Mediated DNA Damage Response |
| title_full | Melatonin Mitigates Cd-Induced Growth Repression and RNA m<sup>6</sup>A Hypermethylation by Triggering MMR-Mediated DNA Damage Response |
| title_fullStr | Melatonin Mitigates Cd-Induced Growth Repression and RNA m<sup>6</sup>A Hypermethylation by Triggering MMR-Mediated DNA Damage Response |
| title_full_unstemmed | Melatonin Mitigates Cd-Induced Growth Repression and RNA m<sup>6</sup>A Hypermethylation by Triggering MMR-Mediated DNA Damage Response |
| title_short | Melatonin Mitigates Cd-Induced Growth Repression and RNA m<sup>6</sup>A Hypermethylation by Triggering MMR-Mediated DNA Damage Response |
| title_sort | melatonin mitigates cd induced growth repression and rna m sup 6 sup a hypermethylation by triggering mmr mediated dna damage response |
| topic | Cd toxicology RNA m<sup>6</sup>A methylation DNA repair cell cycle Arabidopsis |
| url | https://www.mdpi.com/2223-7747/14/9/1398 |
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