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

By M. Cabili, Cole Trapnell, L. Goff, Magdalena J. Koziol, B. Tazón-Vega, Aviv Regev, Johannes Rinn. Genes & Development, 2011

3,378 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/35f337ffea4bc7e55966c84a90b96d28fd7c77a7

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Citations in the corpus

LincRNA-p21 suppresses target mRNA translation. (2012, background): “Among these, the vast majority were lncRNAs, including lincRNA-p21, MALAT1, NEAT1, and lncRNAs involved in X chromosome inactivation (Cabili et al., 2011; Mukherjee et al., 2011).”
Proteogenomics: concepts, applications, and computational strategies (2014, background): “17) or the Broad Institute of MIT and Harvard’s collection of large intergenic noncoding RNAs and transcripts of unknown coding potential 45 (used in ref.”
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Mechanisms of long noncoding RNA function in development and disease (2016, background): “Like mRNAs, lncRNAs are transcribed by Polymerase II, mostly 50-capped, polyadenylated and spliced, though on average they contain a lower number of exons than mRNAs and their expression level assessed across different tissues is lower [3, 4].”
Genomic positional conservation identifies topological anchor point (tap)RNAs linked to developmental loci (2016, background): “…after treatment with differentiating agents, consistent with previous observations by us and others that show co-regulation of lncRNAs and neighboring genes in different species (e.g. (Cabili et al., 2011; Dinger et al., 2008; Goff et al., 2015; Hezroni et al., 2015; Mercer et al., 2008)).”
Non-coding RNAs in disease: from mechanisms to therapeutics (2023, neutral): “several times lower than mRNAs 49,50 . lncRNAs often show high tissue specificity and their expression alters dynamically during development 51 .”
Towards a complete map of the human long non-coding RNA transcriptome (2018, neutral): “this is not to say that annotations should not be rigorously screened to flag “transcripts of unknown coding potential” (ReF.(134)).”
LNCipedia: a database for annotated human lncRNA transcript sequences and structures (2012, background): “In comparison with their protein-coding counterparts, lncRNA genes are poorly conserved (2) and are more numerous in biologically complex species (3).”
Long noncoding RNAs and the genetics of cancer (2013, background): “Long noncoding RNAs are typically more cell-type specific than protein-coding genes (Cabili et al, 2011) and may allow estimation of the cellular composition of a tumour by marking a specific cell population (e.g., cancer stem cells) (Chan et al, 2013).”
GENCODE: The reference human genome annotation for The ENCODE Project (2012, methodology): “In addition, Cabili et al. (2011) have found 2798 lincRNAs not in GENCODE 4 using a combination of HBM RNA-seq and additional RNA-seq from eight additional cell lines and tissues totaling 4 billion reads.”
The Xist lncRNA exploits three-dimensional genome architecture to spread across the X-chromosome (2013, background): “Mammalian genomes encode thousands of large non-coding RNAs (lncRNAs) (1-5), many of which play key functional roles in the cell (6-9).”