Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses

TLDR

Large intergenic noncoding RNAs (lincRNAs) are emerging regulators of diverse cellular processes, yet their individual functions remain difficult to determine; recent RNA‑seq and computational advances enable unprecedented transcript analysis. The study aims to create a comprehensive reference catalog of over 8,000 human lincRNAs. The authors integrated existing annotations with 4 billion RNA‑seq reads from 24 tissues to assemble a catalog and profiled each lincRNA using more than 30 sequence, structural, transcriptional, and orthology features. They found that lincRNAs exhibit highly tissue‑specific expression, co‑express with neighboring genes similarly to coding genes, and identified a conserved subset that may encode short peptides; the resulting catalog elucidates global lincRNA properties and supports future functional studies.

Abstract

Large intergenic noncoding 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 catalog of >8000 human lincRNAs. Our catalog 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 >30 properties, including sequence, structural, transcriptional, and orthology features. We found that lincRNA expression is strikingly tissue-specific compared with coding genes, and that lincRNAs are typically coexpressed with their neighboring genes, albeit to an extent similar to that of pairs of neighboring protein-coding genes. We distinguish an additional subset of transcripts that have high evolutionary conservation but may include short ORFs and may serve as either lincRNAs or small peptides. Our integrated, comprehensive, yet conservative reference catalog of human lincRNAs reveals the global properties of lincRNAs and will facilitate experimental studies and further functional classification of these genes.