N6-Methyladenosine Methylome Profiling of Muscle and Adipose Tissues Reveals Methylase–mRNA Metabolic Regulatory Networks in Fat Deposition of Rex Rabbits

SIMPLE SUMMARY: N6-methyladenosine is the most prevalent internal form of modification found in recent years and plays an important role in gene regulation, which can regulate many physiological processes, such as fat deposition, immunity, and reproduction. The intramuscular fat content is an important problem to be solved in the development of animal husbandry. In order to find a way to increase the intramuscular fat content of Rex rabbit muscles, we explored the methylation modification genes related to fat deposition in Rex rabbit muscle and adipose tissue. We found 5 differential methylases and 12 key genes for methylation modification related to fat deposition between muscle and adipose tissues samples. In addition, five differential methylases were found to regulate adipogenesis by affecting the expression of screened genes in different ways. These findings provided a theoretical basis for our future research on the function of methylation modification during the growth of fat deposits and provided a new way to increase intramuscular fat in Rex rabbits. ABSTRACT: N6-methyladenosine (m(6)A) is the most prevalent internal form of modification in messenger RNA in higher eukaryotes and plays an important role in cancer, immunity, reproduction, development, and fat deposition. Intramuscular fat is the main factor used to measure the meat quality of an animal. The deposition of intramuscular fat and perirenal fat increases with age. However, there is no data on m(6)A modification of Rex rabbits and its potential biological roles in adipose deposition and muscle growth. Here, we performed two high-throughput sequencing methods, m(6)A-modified RNA immunoprecipitation sequence (MeRIP-seq) and RNA sequence (RNA-seq), to identify key genes with m(6)A modification on fat deposition in the muscle and adipose tissues of Rex rabbits. Then, qRT-PCR was used to identify the differently methylated genes related to fat deposition. Our findings showed that there were 12,876 and 10,973 m(6)A peaks in the rabbit muscle and adipose tissue transcriptomes, respectively. Stop codons, 3′-untranslated regions, and coding regions were found to be mainly enriched for m(6)A peaks. In addition, we found 5 differential methylases and 12 key genes of methylation modification related to fat deposition between muscle and adipose tissues samples. The expression levels of six random key genes were significantly higher in the fat than that in the muscle of Rex rabbits at different stages (p < 0.01). Finally, five differential methylases were found to regulate adipogenesis by affecting the expression of screened genes in different ways. These findings provided a theoretical basis for our future research on the function of m(6)A modification during the growth of fat deposits.