Conserved regions in long non-coding RNAs contain abundant translation and protein–RNA interaction signatures

The mammalian transcriptome includes thousands of transcripts that do not correspond to annotated protein-coding genes and that are known as long non-coding RNAs (lncRNAs). A handful of lncRNAs have well-characterized regulatory functions but the biological significance of the majority of them is not well understood. LncRNAs that are conserved between mice and humans are likely to be enriched in functional sequences. Here, we investigate the presence of different types of ribosome profiling signatures in lncRNAs and how they relate to sequence conservation. We find that lncRNA-conserved regions contain three times more ORFs with translation evidence than non-conserved ones, and identify nine cases that display significant sequence constraints at the amino acid sequence level. The study also reveals that conserved regions in intergenic lncRNAs are significantly enriched in protein–RNA interaction signatures when compared to non-conserved ones; this includes sites in well-characterized lncRNAs, such as Cyrano, Malat1, Neat1 and Meg3, as well as in tens of lncRNAs of unknown function. This work illustrates how the analysis of ribosome profiling data coupled with evolutionary analysis provides new opportunities to explore the lncRNA functional landscape.