Global N6-methyladenosine methylation analysis reveals the positive correlation between m6A modification and mRNA abundance during Apostichopus japonicus disease development

N 6 -methyladenosine (m 6 A), the most abundant epitranscriptomic modification in eukaryotic messenger RNA (mRNA), plays important roles in regulation of gene expression for fundamental biological processes and diverse physiological functions, including combating with pathogen infection. Here, we were first profile transcriptome-wide m 6 A sequencing in four stages of skin ulceration syndrome-diseased Apostichopus japonicus following Vibrio splendidus infection, including Control (healthy), Early (small ulcer), Later (extensive ulcer), and Resistant (no ulcer) groups. Our results revealed that three experimental groups were all extensively methylated by m 6 A and the proportion of the m 6 A modified genes were also significantly increased to 28.90% (Early), 27.97% (Later), and 29.98% (Resistant) when compared with Control group (15.15%), indicating m 6 A modification could be induced by V. splendidus infection. Intriguingly, we discovered a positive correlation between the m 6 A methylation level and mRNA abundance, indicating a positive regulatory role of m 6 A in sea cucumber gene expression during V. splendidus infection. Moreover, genes with specific and differentially expressed m 6 A methylation in Later group were both enriched in cell adhesion, while Early and Resistant groups were both mainly involved in DNA conformation change and chromosome organization when compared with Control, suggesting the higher-methylated m 6 A might serve as “conformational marker” and associated to the initiation of related anti-disease genes transcription in order to improve disease resistance of sea cucumber. Subsequently, we selected the pivotal genes enriched in cell adhesion pathway and found that the IggFc-binding protein (FcGBP) and Fibrocystin-L both had higher levels of m 6 A methylation and higher level of mRNA expressions in Later group. Conversely, Fibrinogen C domain-containing protein 1 (F1BCD1) gene presented as an antibacterial role in sea cucumber and showed higher mRNA expression and higher m 6 A methylation in Resistant group and lower mRNA level in Later group. The levels of m 6 A methylation and mRNA abundance of FcGBP and F1BCD1 genes indicates disease occurrence or disease resistant were also verified by MeRIP-qPCR. Overall, our study presents the first comprehensive characterize of dynamic m 6 A methylation modification in the different stages of disease in sea cucumber. These data provide an invaluable resource for future studies of function and biological significance of m 6 A in mRNA in marine invertebrates. • The transcriptome-wide m 6 A sequencing was performed in Apostichopus japonicus at four different stages during SUS disease progression. • m 6 A methylation were highly enriched in three experimental groups following Vibrio splendidus infection. • A positive correlation between the m 6 A methylation level and mRNA abundance was detected. • m 6 A methylated genes in Later was enriched in cell adhesion pathway, while in Early and Resistant groups were involved in DNA conformation change. • The levels of m 6 A methylation and mRNA abundance of FcGBP and F1BCD1 genes were verified by MeRIP-qPCR.