Melatonin Mitigates Cd-Induced Growth Repression and RNA mA 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 mA methylation. We aimed to elucidate the effect of MT on growth repression and RNA mA methylation in Arabidopsis () 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 and mutants, respectively. With distinct dose-effect relationships, mA hypermethylation responded to Cd stress rather than Cu stress, which was further elevated in MMR-deficient seedlings. MT reduced mA levels by 22.98% even without stress induction, whereas the depressed mA levels in MMR-deficient seedlings, greatly exceeding those in the WT. The "writer" and "eraser" gene expression responsible for mA methylation was reduced with the concentration of stresses due to MT, but and no longer responded to Cd stress in and . 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 mA methylation regulation, which shed light on Cd phytoremediation.