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Nature. 2017 Mar 9;543(7644):199-204. doi: 10.1038/nature21374. Epub 2017 Mar 1.

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

Author information

1
RIKEN Center for Life Science Technologies (Division of Genomic Technologies), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045 Japan.
2
RIKEN Omics Science Center (OSC), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
3
Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, 14 Medical Drive, #12-01, Singapore 117599, Singapore.
4
University of Bristol, Department of Computer Science, Life Sciences building, 24 Tyndall Avenue, Bristol BS8 1TQ, UK.
5
Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, 8 College Road, 169857 Singapore.
6
Institute of Natural and Mathematical Sciences, Massey University Auckland, Albany 0632, New Zealand.
7
Biotechnology Research Institute for Drug Discovery (BRD), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 2, 1-1-1 Umezono, Tsukuba, Ibaraki, 305-8568, Japan.
8
RIKEN Preventive Medicine and Diagnosis Innovation Program, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
9
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA.
10
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain.
11
Universitat Pompeu Fabra (UPF), Barcelona Biomedical Research Park (PRBB), Dr Aiguader 88, Barcelona 08003, Spain.
12
Computational Bioscience Research Center; Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
13
Institute of Bioengineering, Research Center of Biotechnology RAS, Moscow 119071, Russia.
14
Vavilov Institute of General Genetic, RAS, Moscow 119991, Russia.
15
Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, the University of Western Australia, Nedlands 6009, Western Australia, Australia.
16
Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan 48201, USA.
17
Department of Neurology, School of Medicine, Wayne State University, Detroit, Michigan 48201, USA.
18
Telethon Kids Institute, The University of Western Australia, 100 Roberts Road, Subiaco, Subiaco, 6008, Western Australia, Australia.
19
German Center for Neurodegenerative Diseases (DZNE), D-72076 Tübingen, Germany.
20
Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.
21
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane 4072, Australia.
22
Faculty of Medicine, Department of Anatomy and Neuroscience, The University of Melbourne, 3010, Australia.
23
RIKEN CLST (Division of Bio-Function Dynamics Imaging), Wako, Saitama 351-0198, Japan.
24
Cell Engineering Division, RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.
25
Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan.
26
Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Huddinge, Sweden.

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.

PMID:
28241135
DOI:
10.1038/nature21374
[Indexed for MEDLINE]

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