Abstract
Bulk sequencing of RNA transcripts has typically been used to quantify gene expression levels in different experimental systems. However, linking differentially expressed (DE) mRNA transcripts to gene expression regulators, such as miRNAs, remains challenging, as miRNA-mRNA interactions are commonly identified post hoc after selecting sets of genes of interest, thus biasing the interpretation of underlying gene regulatory networks. In this study, we aimed at disentangling miRNA-driven post-transcriptional signals linked to porcine muscle and adipose tissue energy homeostasis. For this purpose, we performed an exon-intron split analysis (EISA) on muscle and fat RNA-seq data from two independent pig populations. One of these populations was subjected to fasting-feeding conditions, while the other represented divergent fatness profiles. After running EISA, protein-coding mRNA genes with downregulated exonic fractions and high post-transcriptional signals were significantly enriched for binding sites of DE upregulated miRNAs. Moreover, these downregulated genes showed an increased expression covariation for the exonic fraction compared to the intronic fraction. On the contrary, they did not show enrichment for binding sites of non-DE highly expressed or downregulated DE miRNAs. Among the set of loci displaying miRNA-driven post-transcriptional regulatory signals, we observed genes related to glucose homeostasis (DKK2, PDK4, IL18, NR4A3, CHRNA1, TET2), cell differentiation (PBX1, BACH2) and adipocytes metabolism (SESN3, ESRRG, SAMD4, LEP, PTGFR, SERPINE2, RNF157, GPLD1, NCF2, OSBPL10, PRSS23). Our results highlighted mRNA genes showing post-transcriptional miRNA-driven downregulation using the exonic and intronic fractions of RNA-seq datasets from muscle and adipose tissues in pigs.