Abstract
Several recent studies have demonstrated the role of long non-coding RNAs (lncRNAs) in regulating the defense mechanism against parasite infections, but no studies are available that investigated their relevance for immune response to nematode infection in sheep. Thus, the aim of the current study was to (i) detect putative lncRNAs that are expressed in the abomasal lymph node of adult sheep after an experimental infection with the gastrointestinal nematode (GIN) Teladorsagia circumcincta and (ii) to elucidate their potential functional role associated with the differential host immune response. We hypothesized that putative lncRNAs differentially expressed (DE) between samples from animals that differ in resistance to infection may play a significant regulatory role in response to nematode infection in adult sheep. To obtain further support for our hypothesis, we performed co-expression and functional gene enrichment analyses with the differentially expressed lncRNAs (DE lncRNAs). In a conservative approach, we included for this predictive analysis only those lncRNAs that are confirmed and supported by documentation of expression in gastrointestinal tissues in the current sheep gene atlas. We identified 9,105 putative lncRNA transcripts corresponding to 7,124 gene loci. Of these, 457 were differentially expressed lncRNA loci (DELs) with 683 lncRNA transcripts. Based on a gene co-expression analysis via weighted gene co-expression network analysis, 12 gene network modules (GNMs) were found significantly correlated with at least one of 10 selected target DE lncRNAs. Based on the principle of “guilt-by-association,” the DE genes from each of the three most significantly correlated GNMs were subjected to a gene enrichment analysis. The significant pathways associated with DE lncRNAs included ERK5 Signaling, SAPK/JNK Signaling, RhoGDI Signaling, EIF2 Signaling, Regulation of eIF4 and p70S6K Signaling and Oxidative Phosphorylation pathways. They belong to signaling pathway categories like Cellular Growth, Proliferation and Development, Cellular Stress and Injury, Intracellular and Second Messenger Signaling and Apoptosis. Overall, this lncRNA study conducted in adult sheep after GIN infection provided first insights into the potential functional role of lncRNAs in the differential host response to nematode infection.
Highlights
The central dogma of molecular biology states that DNA is transcribed into mRNA and mRNA is translated into protein products (Crick, 1970)
The aim of the current study was to detect long non-coding RNAs (lncRNAs) in the transcriptome of abomasal lymph node (ALN) tissue samples extracted from adult Spanish Churra sheep after an experimental infection with the gastrointestinal nematode (GIN) Teladorsagia circumcincta and to elucidate their potential functional role associated with the host immune response against GIN infection in adult sheep
LncRNAs are known to play multiple biological functions and their expression varies with the developmental stage of cells and tissues and under different disease states and environmental challenges (Ma et al, 2012)
Summary
The central dogma of molecular biology states that DNA is transcribed into mRNA and mRNA is translated into protein products (Crick, 1970). There is an increasing interest, in the non-protein coding RNAs (ncRNAs), which are estimated to comprise up to 80% of the entire transcriptome in mammals (The ENCODE Project Consortium, 2012; Hon et al, 2017; Srijyothi et al, 2018). LncRNAs are biochemically resembling mRNAs, they generally do not encode protein products (Ponting et al, 2009). LncRNAs are divided into several subgroups according to the positional genomic relationship between lncRNAs and their neighboring protein-coding genes including overlapping, antisense, intronic and intergenic lncRNAs. Advances in computational biology and evolution of sensitive RNA sequencing and epigenomic technologies have facilitated the discovery of numerous lncRNAs and encouraged the study of their functional roles
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