Convention tells us that ‘DNA makes RNA makes protein’, but the function of the majority of RNA that does not code for protein has, historically, been less clear. The recent advent of high-throughput sequencing technology has challenged our preconceptions of long non-coding RNA (lncRNA) and revealed it to be one of the most abundant RNA molecules. Although only a small number of lncRNAs have been well characterised, they appear to be crucial in the control of gene expression pathways and are no longer considered ‘transcriptional noise’.
Found mostly within introns, sno-lncRNA is an elusive class of lncRNA that depends on snoRNA (small nucleolar RNA) at both ends for its processing. The genomic region encoding one abundant class of sno-lncRNAs is specifically deleted in those with Prader-Willi Syndrome (PWS), a rare genetic disorder in humans. But despite evidence for such apparent functionality, studies identifying and characterising sno-lncRNAs across the genome are lacking. This has been addressed in a recent study published in BMC Genomics by Li Yang from the Key Laboratory of Computational Biology at the CAS-MPG Partner Institute for Computational Biology, China, and colleagues.
Using available data and a series of bioinformatic tools, Yang and colleagues identified sno-lncRNAs across the human, rhesus monkey and mouse genomes. They annotated pairs of snoRNAs and used a custom computational pipeline to identify 19 expressed sno-lncRNAs. Primary sequence analysis revealed that while they do have highly conserved snoRNA ends, sno-lncRNAs themselves are not well conserved.
Within the PWS region, it was found that sno-lncRNAs were highly expressed in the human genome, somewhat expressed in rhesus and undetectable in mouse, indicating that mice might make unsuitable models to study human PWS. They also found one sno-lncRNA in the RPL13A region of the embryonic stem cell of the mouse. RPL13A is a gene encoding a ribosomal protein, and is associated with the regulation of lipid toxicity. Further analyses of PWS and RPL13A region sno-lncRNAs indicated that their expression is species-specific and results from alternative splicing, whereby a single gene can be spliced to code for multiple proteins.
Complex organisms are awash with non-protein-coding RNA, whose regulatory roles appear to be many and varied. This study brings us one step closer to understanding one of the most elusive of the non-coding RNAs and further demonstrates a complex regulatory network of coding and non-coding parts within the mammalian genome.