Cadmium exposure elicited dynamic RNA mA modification and epi-transcriptomic regulation in the Pacific whiteleg shrimp Litopenaeus vannamei.

N6-methyladenosine (mA) methylation is the most prevalent post-transcriptional RNA modification in eukaryotic organisms, but its roles in the regulation of physiological resistance of marine crustaceans to heavy metal pollutants are poorly understood. In this study, the transcriptome-wide mA RNA methylation profiles and dynamic mA changes induced by acute Cd exposure in the the pacific whiteleg shrimp Litopenaeus vannamei were comprehensively analyzed. Cd toxicity caused a significant reduction in global RNA mA methylation level, with major mA regulators including the mA methyltransferase METTL3 and the mA binding protein YTHDF2 showing declined expression. Totally, 11,467 mA methylation peaks from 6415 genes and 17,291 peaks within 7855 genes were identified from the Cd exposure group and the control group, respectively. These mA peaks were predominantly enriched in the 3' untranslated region (UTR) and around the start codon region of the transcripts. 7132 differentially expressed genes (DEGs) and 7382 differentially mA-methylated genes (DMGs) were identified. 3186 genes showed significant changes in both gene expression and mA methylation levels upon cadmium exposure, and they were related to a variety of biological processes and gene pathways. Notably, an array of genes associated with antioxidation homeostasis, transmembrane transporter activity and intracellular detoxification processes were significantly enriched, demonstrating that mA modification may mediate the physiological responses of shrimp to cadmium toxicity via regulating ROS balance, Cd transport and toxicity mitigation. The study would contribute to a deeper understanding of the evolutionary and functional significance of mA methylation to the physiological resilience of decapod crustaceans to heavy metal toxicants.