Profiling of N6-methyladenosine methylation in porcine longissimus dorsi muscle and unravelling the hub gene ADIPOQ promotes adipogenesis in an m6A-YTHDF1–dependent manner

Abstract

Abstract BackgroundIntramuscular fat (IMF) content is critical indicator of pork quality, and abnormal IMF is also relevant to human disease as well as aging. Although N6-methyladenosine (m6A) RNA modification was recently found to regulate adipogenesis in porcine intramuscular fat, however, the understanding of underlying molecular mechanism was still limited. ResultsIn this work, we collected 20 longissimus dorsi muscle (LDM) samples with high and low IMF content from a unique heterogenous swine population for m6A sequencing (m6A-seq). We discovered 70 genes show both differential RNA expression and m6A modification, including ADIPOQ and SFRP1, two hub genes inferred through gene co-expression analysis. Particularly, we observed ADIPOQ, contains 3 m6A modification sites within 3’ untranslated and protein coding region, could promote porcine intramuscular preadipocyte differentiation in an m6A-dependent manner. Furthermore, we found the YTH domain family protein 1 (YTHDF1) could target and promote ADIPOQ mRNA translation. ConclusionOur study provided a comprehensive profiling of m6A methylation in porcine LDM, and characterized the involvement of m6A epigenetic modification on ADIPOQ mRNA in regulation of IMF deposition through an m6A-YTHDF1-dependent manner.