Long noncoding RNAs (lncRNAs) dynamics evidence immunomodulation during ISAV-Infected Atlantic salmon (Salmo salar) (original) (raw)

Despite evidence for participation in the host response to infection, the roles of many long non-coding RNAs (lncRNAs) remain unknown. Therefore, the aims of this study were to identify lncRNAs in Atlantic salmon (Salmo salar) and evaluate their transcriptomic regulation during ISA virus (ISAV) infection, an Orthomyxoviridae virus associated with high mortalities in salmonid aquaculture. Using next-generation sequencing, whole-transcriptome analysis of the Salmo salar response to ISAV infection was performed, identifying 5,636 putative lncRNAs with a mean length of 695 base pairs. The transcriptional modulation evidenced a similar number of differentially expressed lncRNAs in the gills (3,294), head-kidney (3,275), and liver (3,325) over the course of the infection. Moreover, analysis of a subset of these lncRNAs showed the following: (i) Most were similarly regulated in response to ISA virus infection; (ii) The transcript subsets were uniquely modulated in each tissue (gills, liver, and head-kidney); and (iii) A subset of lncRNAs were upregulated for each tissue and time analysed, indicating potential markers for ISAV infection. These findings represent the first discovery of widespread differential expression of lncRNAs in response to virus infection in non-model species, suggesting that lncRNAs could be involved in regulating the host response during ISAV infection. Large-scale transcriptomic studies have led to surprising discoveries, including that <10% of the mammalian genome is dedicated to protein coding and that the genome contains a vast amount of non-protein coding transcripts, which has resulted in debate about the role of non-coding RNAs (ncRNAs) in cell biology 1,2. In contrast to protein coding genes, it is possible that the non-coding portion of the genome is related to organism complexity and crucial regulatory processes 3,4. Traditionally, the regulatory functions of RNA were thought limited to roles as ribosomal, messenger, and transfer RNAs. However, ncRNAs have been classified as housekeeping RNAs, microRNAs, small interfering RNAs, PIWI-interacting RNAs, small ncRNAs (< 200 nucleotides [nt] in length), and long ncRNAs (lncRNAs, > 200 nt in length) 5. Specifically, lncRNAs are endogenous cellular RNAs that are mRNA-like in length but with an absent or reduced coding potential (open reading frames (ORF) > 30 amino acids). These RNAs include tens of thousands of polyadenylated and non-polyadenylated lncRNAs that are anti-sense, intronic, intergenic, and that overlap with protein coding loci 5. Once thought to be transcriptional noise, lncRNAs have been shown to regulate a variety of biological processes. While the complex paradigm of RNA-based gene regulation is slowly being revealed, there is a growing body of evidence for a central role of lncRNAs in controlling gene regulation 6,7. A recent review estimated that the total number of lncRNAs is likely ~20,000 transcripts, but, to date, only ~200 lncRNAs have been characterized 8 .