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

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. TestaLeonard Lipovich, Chi-Wai Yip, Imad Abugessaisa, Mickaël Mendez, Akira Hasegawa, Dave Tang, Timo Lassmann, Peter Heutink, Magda Babina, Christine A. Wells, Soichi Kojima, Yukio Nakamura, Harukazu Suzuki, Carsten O. Daub, Michiel J. L. de Hoon, Erik Arner, Yoshihide Hayashizaki, Piero Carninci, Alistair R. R. Forrest

Research output: Contribution to journalArticlepeer-review

608 Scopus citations

Abstract

Long non-coding RNAs (lncRNAs) are largely heterogeneous and functionally uncharacterized. Here, using FANTOM5 cap analysis of gene expression (CAGE) data, we integrate multiple transcript collections to generate a comprehensive atlas of 27,919 human lncRNA genes with high-confidence 5′ ends and expression profiles across 1,829 samples from the major human primary cell types and tissues. Genomic and epigenomic classification of these lncRNAs reveals that most intergenic lncRNAs originate from enhancers rather than from promoters. Incorporating genetic and expression data, we show that lncRNAs overlapping trait-associated single nucleotide polymorphisms are specifically expressed in cell types relevant to the traits, implicating these lncRNAs in multiple diseases. We further demonstrate that lncRNAs overlapping expression quantitative trait loci (eQTL)-associated single nucleotide polymorphisms of messenger RNAs are co-expressed with the corresponding messenger RNAs, suggesting their potential roles in transcriptional regulation. Combining these findings with conservation data, we identify 19,175 potentially functional lncRNAs in the human genome.
Original languageEnglish (US)
Pages (from-to)199-204
Number of pages6
JournalNature
Volume543
Issue number7644
DOIs
StatePublished - Mar 1 2017

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: FANTOM5 was made possible by research grants for the RIKEN Omics Science Center and the Innovative Cell Biology by Innovative Technology (Cell Innovation Program) from the MEXT to Y.H. It was also supported by research grants for the RIKEN Preventive Medicine and Diagnosis Innovation Program (RIKEN PMI) to Y.H. and the RIKEN Centre for Life Science Technologies, Division of Genomic Technologies (RIKEN CLST (DGT)) from the MEXT, Japan. A.R.R.F. is supported by a Senior Cancer Research Fellowship from the Cancer Research Trust, the MACA Ride to Conquer Cancer and the Australian Research Council’s Discovery Projects funding scheme (DP160101960). S.D. is supported by award number U54HG007004 from the National Human Genome Research Institute of the National Institutes of Health, funding from the Ministry of Economy and Competitiveness (MINECO) under grant number BIO2011-26205, and SEV-2012-0208 from the Spanish Ministry of Economy and Competitiveness. Y.A.M. is supported by the Russian Science Foundation, grant 15-14-30002. We thank RIKEN GeNAS for generation of the CAGE and RNA-seq libraries, the Netherlands Brain Bank for brain materials, the RIKEN BioResource Centre for providing cell lines and all members of the FANTOM5 consortium for discussions, in particular H. Ashoor, M. Frith, R. Guigo, A. Tanzer, E. Wood, H. Jia, K. Bailie, J. Harrow, E. Valen, R. Andersson, K. Vitting-Seerup, A. Sandelin, M. Taylor, J. Shin, R. Mori, C. Mungall and T. Meehan.

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