An atlas of human long non-coding RNAs with accurate 5' ends

An atlas of human long non-coding RNAs with accurate 5' ends

2017 March 09 | Chung-Chau Hon, Jordan A. Ramilowski, Jayson Harshbarger, Nicolas Bertin, Owen J. L. Rackham, Julian Gough, Elena Denisenko, Sebastian Schmeier, Thomas M. Poulsen, Jessica Severin, Marina Lizio, Hideya Kawaji, Takeya Kasukawa, Masayoshi Itoh, A. Maxwell Burroughs, Shohei Noma, Sarah Djebali, Tanvir Alam, Yulia A. Medvedeva, Alison C. Testa, Leonard Lipovich, Chi-Wai Yip, Imad Abugessais, Mickaël Mendez, Akira Hasegawa, Dave Tang, Timo Lassmann, Peter Heutink, Magda Babina, Christine A. Wells, Soichi Koijima, Yukio Nakamura, Harukazu Suzuki, Carsten O. Daub, Michiel J. L. de Hoon, Erik Arner, Yoshihide Hayashizaki, Piero Carninci, Alistair R. R. Forrest
A comprehensive atlas of human long non-coding RNAs (lncRNAs) with accurate 5' ends was generated using FANTOM5 cap analysis of gene expression (CAGE) data. This atlas includes 27,919 human lncRNA genes with high-confidence 5' ends and expression profiles across 1,829 samples from major human primary cell types and tissues. The study integrates genomic and epigenomic data to classify lncRNAs, revealing that most intergenic lncRNAs originate from enhancers rather than promoters. The analysis shows that lncRNAs overlapping trait-associated single nucleotide polymorphisms (SNPs) are specifically expressed in cell types relevant to the traits, suggesting their involvement in multiple diseases. Additionally, lncRNAs overlapping expression quantitative trait loci (eQTL)-associated SNPs are co-expressed with corresponding messenger RNAs, indicating potential roles in transcriptional regulation. Combining these findings with conservation data, the study identifies 19,175 potentially functional lncRNAs in the human genome. The study also explores the diversity and functional relevance of lncRNAs, highlighting that intergenic p-lncRNAs, such as MALAT1, are a minority compared to intergenic e-lncRNAs and divergent p-lncRNAs. The analysis reveals that lncRNAs with conserved exons, TIRs, and associations with GWAS traits or eQTLs are more likely to be functional. The study further identifies that lncRNAs implicated in GWAS traits and eQTLs show significant enrichment of conserved regions, supporting their functional relevance. The results suggest that lncRNAs contribute substantially to the specific associations between related cell types and traits. The study provides a comprehensive resource for prioritizing lncRNA candidates for functional studies, emphasizing the potential functionality of 69% of the FANTOM CAT lncRNAs. The findings advance the understanding of the functional relevance of pervasive transcription from mammalian genomes.A comprehensive atlas of human long non-coding RNAs (lncRNAs) with accurate 5' ends was generated using FANTOM5 cap analysis of gene expression (CAGE) data. This atlas includes 27,919 human lncRNA genes with high-confidence 5' ends and expression profiles across 1,829 samples from major human primary cell types and tissues. The study integrates genomic and epigenomic data to classify lncRNAs, revealing that most intergenic lncRNAs originate from enhancers rather than promoters. The analysis shows that lncRNAs overlapping trait-associated single nucleotide polymorphisms (SNPs) are specifically expressed in cell types relevant to the traits, suggesting their involvement in multiple diseases. Additionally, lncRNAs overlapping expression quantitative trait loci (eQTL)-associated SNPs are co-expressed with corresponding messenger RNAs, indicating potential roles in transcriptional regulation. Combining these findings with conservation data, the study identifies 19,175 potentially functional lncRNAs in the human genome. The study also explores the diversity and functional relevance of lncRNAs, highlighting that intergenic p-lncRNAs, such as MALAT1, are a minority compared to intergenic e-lncRNAs and divergent p-lncRNAs. The analysis reveals that lncRNAs with conserved exons, TIRs, and associations with GWAS traits or eQTLs are more likely to be functional. The study further identifies that lncRNAs implicated in GWAS traits and eQTLs show significant enrichment of conserved regions, supporting their functional relevance. The results suggest that lncRNAs contribute substantially to the specific associations between related cell types and traits. The study provides a comprehensive resource for prioritizing lncRNA candidates for functional studies, emphasizing the potential functionality of 69% of the FANTOM CAT lncRNAs. The findings advance the understanding of the functional relevance of pervasive transcription from mammalian genomes.
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