m⁶A mRNA Methylation Analysis Provides Novel Insights into Pigmentation in Sheep Skin

N6-methyladenosine (m⁶A) is the most universal post-transcriptional modification of mRNA which may play important roles in verious species. However, the potential roles of m⁶A in the pigmentation of skin are not completely understood. To explore the role of m6A modification in pigmentation of sheep skin, we used MeRIP-seq and RNA-seq to profile the skin transcriptome in black and white coat color (<i>n=</i>3). Our results showed that an average of 7701 m⁶A peaks were obtained for all samples and the average length was 305.89 bp. The GGACUU sequence was the most enrichment motif and shared in black skin and white skin. The m⁶A peaks were mainly enriched in the CDS, 3'UTR and 5'UTR, especially in CDS region near the stop codon of the transcript. 235 significantly differential peaks were found in black skin vs. white skin. The KEGG signaling pathways of downregulated and upregulated m⁶A peaks were mainly enriched in AGE-RAGE signaling pathway in diabetic complications, Viral carcinogenesis, Transcriptional misregulation in cancer, ABC transporters, Basal transcription factors and Thyroid hormone synthesis (<i>P</i> value &lt;0.05). For RNA-seq, 71 differently expressed genes (DEGs) were scanned in black skin vs. white skin. DEGs were significantly enriched in tyrosine metabolism, melanogenesis, neuroactive ligand-receptor interaction pathway (<i>P</i> value &lt;0.05). Combined m⁶A-seq and RNA-seq analysis showed that the hyper-up genes and hypo-up genes were both enriched in ErbB signaling pathway (<i>P</i> value &lt;0.05). In conclusion, it provide a basis for further research into the functions of m⁶A methylation modifications in pigmentation.