Role of Long Non-Coding RNAs in Bacterial Cold Water Disease Pathogenesis in Rainbow Trout

Background: Bacterial cold water disease (BCWD) caused by Flavobacterium psychrophilum is one of the major causes of mortality in salmonids. Three genetic lines of rainbow trout designated as ARS-Fp-R (resistant), ARS-Fp-C (control) and ARS-Fp-S (susceptible) have significant differences in survival rate following F. psychrophilum infection. Previous studies have identified transcriptomic differences of immune-relevant protein-coding genes at basal and post-infection levels among these genetic lines. Results: Using an RNA-seq approach, we quantified differentially expressed long non-coding RNAs (lncRNAs) in response to F. psychrophilum challenge. Pairwise comparison between genetic lines and different stages of infection identified 705 differentially expressed lncRNAs. A positive correlation was observed between the number of the differentially regulated lncRNAs and that of the protein-coding genes following infection.  Many of the differentially expressed lncRNAs were located near immune-related protein-coding loci. The expression patterns of several lncRNAs were either positively or negatively correlated with those of their neighboring and distant immune related protein-coding genes. The list includes complement components, suppressor of cytokine signaling, tumor necrosis factor receptor superfamily members, chemokines, and transcription factors involved in immunological responsiveness. Most of the protein-coding genes that correlated in expression with lncRNAs were transcription factors, activators, receptors, and molecules of signal transduction pathways related to the innate immune system. The correlated expression and genome-wide co-localization suggested that some of the lncRNAs may be involved in regulating immune-relevant protein-coding genes. Conclusion: This study provides the first evidence of correlated expression between lncRNAs and immune related protein-coding genes in an important aquaculture species.