Cadmium exposure elicited dynamic RNA m6A modification and epi-transcriptomic regulation in the Pacific whiteleg shrimp Litopenaeus vannamei

Abstract

N6-methyladenosine (m⁶A) 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 m⁶A RNA methylation profiles and dynamic m⁶A changes induced by acute Cd²⁺ exposure in the the pacific whiteleg shrimp Litopenaeus vannamei were comprehensively analyzed. Cd²⁺ toxicity caused a significant reduction in global RNA m⁶A methylation level, with major m⁶A regulators including the m⁶A methyltransferase METTL3 and the m⁶A binding protein YTHDF2 showing declined expression. Totally, 11,467 m⁶A methylation peaks from 6415 genes and 17,291 peaks within 7855 genes were identified from the Cd²⁺ exposure group and the control group, respectively. These m⁶A 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 m⁶A-methylated genes (DMGs) were identified. 3186 genes showed significant changes in both gene expression and m⁶A 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 m⁶A modification may mediate the physiological responses of shrimp to cadmium toxicity via regulating ROS balance, Cd²⁺ transport and toxicity mitigation. The study would contribute to a deeper understanding of the evolutionary and functional significance of m⁶A methylation to the physiological resilience of decapod crustaceans to heavy metal toxicants.