Evolution to the rescue: using comparative genomics to understand long non-coding RNAs

• Published in: Nature reviews. Genetics Vol. 17; no. 10; pp. 601 - 614
• Main Author: Ulitsky, Igor
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2016; Nature Publishing Group
• Subjects: 631/181/735; 631/208/199; 631/208/200; 631/208/212/2019; 631/208/212/2304; 631/337/384/2568; Agriculture; Animal Genetics and Genomics; Animals; Annotations; Bioinformatics; Biomedicine; Cancer Research; Comparative analysis; Evolution, Molecular; Flowers & plants; Forecasts and trends; Gene Function; Genetic research; Genome-wide association studies; Genomes; Genomics; Genomics - methods; Human Genetics; Humans; Methods; MicroRNAs; Molecular Sequence Annotation; review-article; RNA sequencing; RNA, Long Noncoding - classification; RNA, Long Noncoding - genetics; Sequence Analysis, RNA - methods; Transcriptome - genetics
• ISSN: 1471-0056; 1471-0064
• DOI: 10.1038/nrg.2016.85

Key Points Long non-coding RNAs (lncRNAs) are emerging as important regulators in multiple key pathways. Thousands of lncRNA genes have now been identified in dozens of species, including animals, plants and single-celled organisms. Unlike protein-coding genes and non-coding RNAs such as microRNAs, lncRNAs are rapidly lost and gained during evolution, raising questions about how many of them are functional. Within conserved lncRNAs, exon–intron architectures and sequences are also rapidly turned over with only short regions evolving under purifying selection. Across long evolutionary distances, there are numerous lncRNAs that are found in syntenic regions, but exhibit no detectable sequence similarity. These can correspond to loci where only the act of transcription is important, or to lncRNAs that depend on very short sequence elements for their functions. Evolutionary trajectories can be used to classify lncRNAs into groups with different characteristics and probably different modes of action. In most cases tested so far, lncRNA function was maintained across large evolutionary distances even when the lncRNA sequence substantially diverged. Numerous long non-coding RNAs (lncRNAs) have emerged as having important and mechanistically diverse roles in gene regulation. However, for most lncRNAs, evolution is rapid and functions remain uncharacterized. This Review describes how comparative genomics and transcriptomics can provide broad insights into the functional importance and evolutionary trajectories of lncRNAs across species, and offers guidance for cross-species studies of lncRNAs. Long non-coding RNAs (lncRNAs) have emerged in recent years as major players in a multitude of pathways across species, but it remains challenging to understand which of them are important and how their functions are performed. Comparative sequence analysis has been instrumental for studying proteins and small RNAs, but the rapid evolution of lncRNAs poses new challenges that demand new approaches. Here, I review the lessons learned so far from genome-wide mapping and comparisons of lncRNAs across different species. I also discuss how comparative analyses can help us to understand lncRNA function and provide practical considerations for examining functional conservation of lncRNA genes.