Long noncoding RNAs in lipid metabolism: literature review and conservation analysis across species

Abstract

Background: Lipids are important for the cell and organism life since they are major components of membranes, energy reserves and are also signal molecules. The main organs for the energy synthesis and storage are the liver and adipose tissue, both in humans and in more distant species such as chicken. Long noncoding RNAs (lncRNAs) are known to be involved in many biological processes including lipid metabolism.

Results: In this context, this paper provides the most exhaustive list of lncRNAs involved in lipid metabolism with 60 genes identified after an in-depth analysis of the bibliography, while all "review" type articles list a total of 27 genes. These 60 lncRNAs are mainly described in human or mice and only a few of them have a precise described mode-of-action. Because these genes are still named in a non-standard way making such a study tedious, we propose a standard name for this list according to the rules dictated by the HUGO consortium. Moreover, we identified about 10% of lncRNAs which are conserved between mammals and chicken and 2% between mammals and fishes. Finally, we demonstrated that two lncRNA were wrongly considered as lncRNAs in the literature since they are 3' extensions of the closest coding gene.

Conclusions: Such a lncRNAs catalogue can participate to the understanding of the lipid metabolism regulators; it can be useful to better understand the genetic regulation of some human diseases (obesity, hepatic steatosis) or traits of economic interest in livestock species (meat quality, carcass composition). We have no doubt that this first set will be rapidly enriched in coming years.

Keywords: Evolution; Lipid metabolism; Liver; Synteny; lncRNA.

Fig. 1

The different mechanisms of action of lncRNAs. a Mechanisms with effect at transcriptional level, b at post-transcriptional level and (c) on proteins. d LncRNAs with a role as small noncoding RNA host. e LncRNAs with translational activity through a small ORF. In red, lncRNA; in green, mRNA; in blue, miRNA; the green, yellow and blue oval spheres are proteins. The genes in bold are those mentioned in this review, the others are examples from research fields other than lipid metabolism: SAF⁶⁶ and NRON [97]

Fig. 2

HGNC decision tree for naming lncRNAs according to the Wright’s schema [32], here updated by including divergent lncRNA and lncRNA hosting small noncodingRNA

Fig. 3

Verification of the ALDBGALG00000000505049 and FLRL7 gene models with their neighboring SCD and FADS2 genes in chicken and mouse. a, d Model of protein-coding genes are from Ensembl v.92 and models of lncRNA are from the article of Fan et al. [101] that used ALDB v1.0, a lncRNA database (a for ALDBGALG00000000505049) and from the article of Chen et al. [43] that used their own models (d for FLRL7). Primers (black arrows) were design in order to amplify a fragment (red line) specific of lncRNA gene (I), of coding-protein gene (IV), of intergenic region (III) and of a fragment linking both genes (II). The expected sizes have been specified (black for RNA; red for DNA) according to the models. b, e Electrophoretic gels with the lengths of the amplicons, showing the existence of a unique gene, the lncRNA being an extension of the protein-coding gene. c, f New experimentally corrected models for the protein-coding gene

Fig. 4

Genomic conservation in 8 species of the five lncRNA previously found as conserved between human and chicken. a Tree of genome evolution in vertebrates based on Kumar and Hedges studies [107, 108]. b Conservation of the five lncRNA (yellow) through the animal kingdom in relation to their genomic environment: protein-coding gene (blue). The distances between the intergenic entities are in bases

Fig. 5

Expression of lncRNA in embryo, liver, adipose tissue and hypothalamus in human and chicken. a Expression of the 5 lncRNA conserved between human and chicken. b Expression of all lncRNAs (pale colors) in the different tissues against all the 5 lncRNA studied here. Embryo (E), liver (L), adipose tissue (A), hypothalamus (H). Top: expression in human with n = 3 (embryo not represented), bottom: expression in chicken with n = 16. **: p value< 5% ***: p value< 1%