The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression

By Thomas Derrien, Rory Johnson, G. Bussotti, Andrea Tanzer, S. Djebali, Hagen U. Tilgner, G. Guernec, David Martin, A. Merkel, David G. Knowles and 17 more. Genome Research, 2012

4,833 citations recorded by the source corpus.

The human genome contains many thousands of long noncoding RNAs (lncRNAs). While several studies have demonstrated compelling biological and disease roles for individual examples, analytical and experimental approaches to investigate these genes have been hampered by the lack of comprehensive lncRNA annotation. Here, we present and analyze the most complete human lncRNA annotation to date, produced by the GENCODE consortium within the framework of the ENCODE project and comprising 9277 manually annotated genes producing 14,880 transcripts. Our analyses indicate that lncRNAs are generated through pathways similar to that of protein-coding genes, with similar histone-modification profiles, splicing signals, and exon/intron lengths. In contrast to protein-coding genes, however, lncRNAs display a striking bias toward two-exon transcripts, they are predominantly localized in the chromatin and nucleus, and a fraction appear to be preferentially processed into small RNAs. They are under stronger selective pressure than neutrally evolving sequences—particularly in their promoter regions, which display levels of selection comparable to protein-coding genes. Importantly, about one-third seem to have arisen within the primate lineage. Comprehensive analysis of their expression in multiple human organs and brain regions shows that lncRNAs are generally lower expressed than protein-coding genes, and display more tissue-specific expression patterns, with a large fraction of tissue-specific lncRNAs expressed in the brain. Expression correlation analysis indicates that lncRNAs show particularly striking positive correlation with the expression of antisense coding genes. This GENCODE annotation represents a valuable resource for future studies of lncRNAs.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2830cf5a89339af3ccf8cad2a31ac01e027ad2e4

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Citations in the corpus

Topological Organization of Multi-chromosomal Regions by Firre (2014, neutral): “(4) Pulldowns with targeting (RRD, exon 2 or a combination of both) and nontargeting (scrambled)”
Xist nucleates local protein gradients to propagate silencing across the X chromosome (2021, background): “There has been considerable debate about how lncRNAs can robustly regulate gene expression, given that they are often expressed at low levels (Cabili et al., 2015; Derrien et al., 2012).”
LNCcation: lncRNA localization and function (2021, background): “Like mRNAs, the majority of lncRNAs are transcribed by RNA polymerase II (Pol II) and are capped and polyadenylated (Derrien et al., 2012).”
Genomic variant annotation and prioritization with ANNOVAR and wANNOVAR (2015, methodology): “Please note that the gene definition refers to different gene build annotation systems, including RefGene from the National Center for Biotechnology Information (NCBI) 55 , UCSC Known Gene from UCSC 56 , ENSEMBL gene from the ENSEMBL project 57 and GENCODE gene from the GENCODE consortium 58 .”
Transposable Elements Are Major Contributors to the Origin, Diversification, and Regulation of Vertebrate Long Noncoding RNAs (2013, methodology): “[10] reported that human lncRNAs rarely have extensive sequence similarity to each other outside of shared repetitive elements.”
NONCODEv4: exploring the world of long non-coding RNA genes (2013, background): “Because many lncRNAs reside within or overlap protein-coding loci (11), we then classified lncRNAs genes into four categories according to their genomic location in relation to protein-coding genes: antisense, intergenic, sense exonic and sense non-exonic, respectively.”
Non-coding RNA: what is functional and what is junk? (2015, neutral): “Interestingly, introns in lncRNAs tend to be spliced post-transcriptionally, while those in mRNAs tend to be removed co-transcriptionally (Derrien et al., 2012; Tilgner et al., 2012).”
Braveheart, a long non-coding RNA required for cardiovascular lineage commitment (2013, background): “sequence homology searches revealed no clear orthologous Bvht sequence or transcripts in syntenic regions of the human or rat genomes, consistent with the idea that lncRNAs are less conserved than protein-coding genes (Cabili et al., 2011; Derrien et al., 2012).”
CircNet: a database of circular RNAs derived from transcriptome sequencing data (2015, background): “These samples cover research topics ranging from detecting gene variation (37–41) to searching for long non-coding RNAs (42).”
Circular intronic long noncoding RNAs. (2013, background): “Finally, it is known that regulatory lncRNAs are less conserved than protein-coding genes (Cabili et al., 2011; Derrien et al., 2012).”
Noncoding RNA:RNA Regulatory Networks in Cancer (2018, background): “On the other hand, there has been much debate about the possibility of other lncRNAs acting as miRNA decoys, given their preference for nuclear localization [2,166].”
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].”
Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches. (2016, background): “Additionally, lncRNAs are less conserved than miRNAs (14, 96, 220) because they seem to be under more selective pressure especially in their promoter regions (60).”