LncRNAs in domesticated animals: from dog to livestock species

Abstract

Animal genomes are pervasively transcribed into multiple RNA molecules, of which many will not be translated into proteins. One major component of this transcribed non-coding genome is the long non-coding RNAs (lncRNAs), which are defined as transcripts longer than 200 nucleotides with low coding-potential capabilities. Domestic animals constitute a unique resource for studying the genetic and epigenetic basis of phenotypic variations involving protein-coding and non-coding RNAs, such as lncRNAs. This review presents the current knowledge regarding transcriptome-based catalogues of lncRNAs in major domesticated animals (pets and livestock species), covering a broad phylogenetic scale (from dogs to chicken), and in comparison with human and mouse lncRNA catalogues. Furthermore, we describe different methods to extract known or discover novel lncRNAs and explore comparative genomics approaches to strengthen the annotation of lncRNAs. We then detail different strategies contributing to a better understanding of lncRNA functions, from genetic studies such as GWAS to molecular biology experiments and give some case examples in domestic animals. Finally, we discuss the limitations of current lncRNA annotations and suggest research directions to improve them and their functional characterisation.

Fig. 1

Characterization of lncRNA and mRNA gene structures in 5 domesticated animals (dog, horse, cow, pig, and chicken, respectively in dark green, orange, purple, pink, and light green) in comparison with mouse and human annotations (light and dark grey respectively) extracted from Ensembl (v103). A Comparison of the number of lncRNA and mRNA genes, transcripts, and exons (number of lncRNA and mRNA features are indicated on top of each bar). B Boxplot distributions of the length of lncRNA and mRNA transcripts and exons. C ORF coverage of Ensembl-based lncRNAs annotated as protein-coding by the FEELnc program

Fig. 2

Distribution of reads supporting lncRNAs and mRNAs (A) and gene overlap between NCBI and Ensembl resources according to both biotypes (B). A For each gene biotype (lncRNAs in blue and mRNAs in red), the dark, intermediate and light shades correspond to the percentage of reads supporting all expressed genes, 25% of the most expressed genes and the 10 most expressed genes respectively. RNAseq data correspond to the chicken PRJEB28745 project and 4 tissues (adip adipose tissue, livr liver, blod blood, hypt hypothalamus) of the same population (Rhode Island Red). B) Percentages of chicken lncRNA gene overlap—using 1 bp or more—between the GRCg6a—V104 Ensembl and NCBI gene catalogues. Note that these overlaps have been computed at the gene level given the uncertainty of isoform modelling with short-reads as explained in the main text

Fig. 3

Phylogenetic divergence between domesticated species, mouse, and human. A Red numbers correspond to the common ancestor of different species. This tree was generated using the TimeTree database (Kumar et al. 2017). Distances were calculated from estimated molecular time. B. Genomic conservation of 2 lncRNAs (in green) in divergent position extracted from Foissac et al. (Foissac et al. 2019)

Fig. 4

Syntenic conservation of lncRNAs across 7 species. A schema of "1–1" and "n–1" principles of positionally conserved lncRNAs. The "1–1" corresponds to the case of a strict and unique syntenic equivalent in both species located in-between two adjacent "1–1" protein-coding genes. The "n–1" corresponds to the case of multiple lncRNA loci in the analysed species that corresponds to an unique lncRNA in human located between the two "1–1" protein-coding genes. B Number of lncRNA for each homology category across species with numbers of lncRNA loci (in italic) extracted from Ensembl (v104). The "*" indicates the chicken lncRNA-enriched annotation anchored on the v101 (equivalent to v104) Ensembl resource (Jehl et al. 2020)

Fig. 5

Association between transposable elements (TEs) annotated by RepeatMasker and long non-coding RNAs annotated by Ensembl (v103) in 5 genome assemblies (canFam3, equCab3, bosTau9, susScr11 and galGal6). A Proportion of the genome covered by four TEs classes: LINEs, SINEs, LTRs, and DNA_transposons in green, blue, orange, and grey, respectively. B Proportion of Ensembl-based lncRNA transcripts overlapped by TEs for three fractions overlap (≥ 1 nucleotide, ≥ 5%, and ≥ 10% of the lncRNA sequence) in five domesticated species (dog, horse, cow, pig, and chicken, respectively, in dark green, orange, purple, pink, and light green)