Comprehensive Analysis of Long Noncoding RNA Modified by m6 A Methylation in Oxidative and Glycolytic Skeletal Muscles

Abstract

N6-methyladenosine (m6 A) is the most common modification in eukaryotic RNAs. Accumulating evidence shows m6 A methylation plays vital roles in various biological processes, including muscle and fat differentiation. However, there is a lack of research on lncRNAs’ m6 A modification in regulating pig muscle-fiber-type conversion. In this study, we identified novel and differentially expressed lncRNAs in oxidative and glycolytic skeletal muscles through RNA-seq, and further reported the m6 A-methylation patterns of lncRNAs via MeRIP-seq. We found that most lncRNAs have one m6 A peak, and the m6 A peaks were preferentially enriched in the last exon of the lncRNAs. Interestingly, we found that lncRNAs’ m6 A levels were positively correlated with their expression homeostasis and levels. Furthermore, we performed conjoint analysis of MeRIP-seq and RNA-seq data and obtained 305 differentially expressed and differentially m6 A-modified lncRNAs (dmelncRNAs). Through QTL enrichment analysis of dme-lncRNAs and PPI analysis for their cis-genes, we finally identified seven key m6 A-modified lncRNAs that may play a potential role in muscle-fibertype conversion. Notably, inhibition of one of the key lncRNAs, MSTRG.14200.1, delayed satellite cell differentiation and stimulated fast-to-slow muscle-fiber conversion. Our study comprehensively analyzed m6 A modifications on lncRNAs in oxidative and glycolytic skeletal muscles and provided new targets for the study of pig muscle-fiber-type conversion.