Integrative Annotation of Human Large Intergenic Non-Coding RNAs Reveals Global Properties and Specific Subclasses

Large intergenic non-coding RNAs (lincRNAs) are emerging as key regulators of diverse cellular processes. Determining the function of individual lincRNAs remains a challenge. Recent advances in RNA sequencing (RNA-Seq) and computational methods allow for an unprecedented analysis of such transcripts. Here, we present an integrative approach to define a reference catalogue of over 8,000 human lincRNAs. Our catalogue unifies previously existing annotation sources with transcripts we assembled from RNA-Seq data collected from ~4 billion RNA-Seq reads across 24 tissues and cell types. We characterize each lincRNA by a panorama of more than 30 properties, including sequence, structural, transcriptional, and orthology features. We find that lincRNA expression is strikingly tissue specific compared to coding genes, and that they are typically co-expressed with their neighboring genes, albeit to a similar extent to that of pairs of neighboring protein-coding genes. We distinguish an additional sub-set of transcripts that have high evolutionary conservation but may include short open reading frames, and may serve either as lincRNAs or as small peptides. Our integrated, comprehensive, yet conservative reference catalogue of human lincRNAs reveals the global properties of lincRNAs and will facilitate experimental studies and further functional classification of these genes.