Social status regulates the hepatic miRNAome in rainbow trout: Implications for posttranscriptional regulation of metabolic pathways.

Juvenile rainbow trout develop social hierarchies when held in dyads, and the development of socially subordinate (SS) and social dominance (SD) phenotypes in this context has been linked to specific changes in the hepatic energy metabolism of all major macronutrients. Following our recently reported finding that transcript abundance of drosha, a key component of the microRNA (miRNA) biogenesis pathway, is increased in paired juvenile rainbow trout irrespective of social status compared to socially isolated (SI) controls, we here determined global changes of the hepatic miRNA pathway genes in detail at the transcript and protein level. Both SD and SS rainbow trout exhibited increased Ago2 protein abundance compared to SI rainbow trout, suggesting that hepatic miRNA function is increased in rainbow trout maintained in dyads. Given the well-described differences in hepatic intermediary metabolism between SD and SS rainbow trout, and the important role of miRNAs in the posttranscriptional regulation of metabolic pathways, we also identified changes in hepatic miRNA abundance between SS and SD rainbow trout using small RNA next generation sequencing. We identified a total of 24 differentially regulated miRNAs, with 15 miRNAs that exhibited increased expression, and 9 miRNAs that exhibited decreased expression in the liver of SS trout compared to SD trout. To identify potential miRNA-dependent posttranscriptional regulatory pathways important for social status-dependent regulation of hepatic metabolism in rainbow trout, we used an in silico miRNA target prediction and pathway enrichment approach. We identified enrichment for pathways related to metabolism of carbohydrates, lipids and proteins in addition to organelle-specific processes involved in energy metabolism, especially mitochondrial fusion and fission. Select predicted miRNA-mRNA target pairs within these categories were quantitatively analyzed by real-time RT-PCR to validate candidates for future studies that will probe the functional metabolic roles of specific hepatic miRNAs in the development of SD and SS metabolic phenotypes.