Profiling of N6-methyladenosine methylation in porcine longissimus dorsi muscle and unravelling the hub gene ADIPOQ promotes adipogenesis in an m6A-YTHDF1–dependent manner
Huanfa Gong, Tao Gong, Youhua Liu, Yizhen Wang, Xinxia Wang
Abstract
Abstract Background Intramuscular fat (IMF) content is a critical indicator of pork quality, and abnormal IMF is also relevant to human disease as well as aging. Although N6-methyladenosine (m 6 A) RNA modification was recently found to regulate adipogenesis in porcine intramuscular fat, however, the underlying molecular mechanisms was still unclear. Results In this work, we collected 20 longissimus dorsi muscle samples with high (average 3.95%) or low IMF content (average 1.22%) from a unique heterogenous swine population for m 6 A sequencing (m 6 A-seq). We discovered 70 genes show both differential RNA expression and m 6 A modification from high and low IMF group, including ADIPOQ and SFRP1 , two hub genes inferred through gene co-expression analysis. Particularly, we observed ADIPOQ , which contains three m 6 A modification sites within 3′ untranslated and protein coding region, could promote porcine intramuscular preadipocyte differentiation in an m 6 A-dependent manner. Furthermore, we found the YT521‑B homology domain family protein 1 (YTHDF1) could target and promote ADIPOQ mRNA translation. Conclusions Our study provided a comprehensive profiling of m 6 A methylation in porcine longissimus dorsi muscle and characterized the involvement of m 6 A epigenetic modification in the regulation of ADIPOQ mRNA on IMF deposition through an m 6 A-YTHDF1-dependent manner.