Abstract
Bulk sequencing of RNA transcripts has typically been used to quantify gene expression levels and regulatory signals 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. To this end, we performed an exon-intron split analysis (EISA) to muscle and fat RNA-seq data from two Duroc pig populations. One of these populations was subjected to fasting-feeding conditions, while the other one 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 that of 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) or adipocytes metabolism (SESN3, ESRRG, SAMD4, LEP, PTGFR, SERPINE2, RNF157, GPLD1, NCF2, OSBPL10, PRSS23). Our results highlighted mRNA genes showing post-transcriptional miRNA-driven downregulation by using exonic and intronic fractions of RNA-seq datasets from muscle and adipose tissues in pigs.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
A corrected and reduced version after co-author revision.