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

被引:730
作者
Hon, Chung-Chau [1 ]
Ramilowski, Jordan A. [1 ,2 ]
Harshbarger, Jayson [1 ,2 ]
Bertin, Nicolas [2 ,3 ,28 ]
Rackham, Owen J. L. [4 ,5 ]
Gough, Julian [4 ]
Denisenko, Elena [6 ]
Schmeier, Sebastian [6 ]
Poulsen, Thomas M. [7 ]
Severin, Jessica [1 ,2 ]
Lizio, Marina [1 ,2 ]
Kawaji, Hideya [1 ,2 ,8 ]
Kasukawa, Takeya [1 ]
Itoh, Masayoshi [1 ,2 ,8 ]
Burroughs, A. Maxwell [1 ,2 ,9 ]
Noma, Shohei [1 ,2 ]
Djebali, Sarah [10 ,11 ,29 ]
Alam, Tanvir [12 ]
Medvedeva, Yulia A. [13 ,14 ]
Testa, Alison C. [15 ,16 ]
Lipovich, Leonard [17 ,18 ]
Yip, Chi-Wai [1 ]
Abugessaisa, Imad [1 ]
Mendez, Mickael [1 ,2 ,30 ]
Hasegawa, Akira [1 ,2 ]
Tang, Dave [1 ,2 ,19 ]
Lassmann, Timo [1 ,2 ,19 ]
Heutink, Peter [1 ,20 ]
Babina, Magda [21 ]
Wells, Christine A. [22 ,23 ]
Kojima, Soichi [24 ]
Nakamura, Yukio [25 ,26 ]
Suzuki, Harukazu [1 ,2 ]
Daub, Carsten O. [1 ,2 ,27 ]
de Hoon, Michiel J. L. [1 ,2 ]
Arner, Erik [1 ,2 ]
Hayashizaki, Yoshihide [2 ,8 ]
Carninci, Piero [1 ,2 ]
Forrest, Alistair R. R. [1 ,2 ,15 ,16 ]
机构
[1] RIKEN, Ctr Life Sci Technol, Div Gen Technol, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan
[2] RIKEN, Omics Sci Ctr, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan
[3] Natl Univ Singapore, Ctr Translat Med, Canc Sci Inst Singapore, 14 Med Dr 12-01, Singapore 117599, Singapore
[4] Univ Bristol, Dept Comp Sci, Life Sci Bldg,24 Tyndall Ave, Bristol BS8 1TQ, Avon, England
[5] Duke NUS Med Sch, Program Cardiovasc & Metab Disorders, 8 Coll Rd, Singapore 169857, Singapore
[6] Massey Univ Auckland, Inst Nat & Math Sci, Albany 0632, New Zealand
[7] Natl Inst Adv Ind Sci & Technol, Biotechnol Res Inst Drug Discovery BRD, Tsukuba Cent 2,1-1-1 Umezono, Tsukuba, Ibaraki 3058568, Japan
[8] RIKEN, Prevent Med & Diag Innovat Program, 2-1 Hirosawa, Wako, Saitama 3510198, Japan
[9] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA
[10] Barcelona Inst Sci & Technol, Ctr Gen Regulat CRG, Dr Aiguader 88, Barcelona 08003, Spain
[11] UPF, Barcelona Biomed Res Pk PRBB, Dr Aiguader 88, Barcelona 08003, Spain
[12] KAUST, Computat Biosci Res Ctr, Comp Elect & Math Sci & Engn Div, Thuwal 239556900, Saudi Arabia
[13] RAS, Biotechnol Res Ctr, Inst Bioengn, Moscow 119071, Russia
[14] RAS, Vavilov Inst Gen Genet, Moscow 119991, Russia
[15] Univ Western Australia, QEII Med Ctr, Harry Perkins Inst Med Res, Nedlands, WA 6009, Australia
[16] Univ Western Australia, Med Res Ctr, Nedlands, WA 6009, Australia
[17] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA
[18] Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA
[19] Univ Western Australia, Telethon Kids Inst, 100 Roberts Rd, Subiaco, WA 6008, Australia
[20] German Ctr Neurodegenerat Dis DZNE, D-72076 Tubingen, Germany
[21] Charite, Dept Dermatol & Allergy, D-10117 Berlin, Germany
[22] Univ Queensland, Australian Inst Bioengn & Nanotechnol, Brisbane, Qld 4072, Australia
[23] Univ Melbourne, Fac Med, Dept Anat & Neurosci, Melbourne, Vic 3010, Australia
[24] RIKEN, CLST Div Biofunct Dynam Imaging, Wako, Saitama 3510198, Japan
[25] RIKEN, BioResource Ctr, Cell Engn Div, Tsukuba, Ibaraki 3050074, Japan
[26] Univ Tsukuba, Fac Med, Tsukuba, Ibaraki 3058577, Japan
[27] Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden
[28] Human Longev Singapore Pte Ltd, Singapore, Singapore
[29] Univ Toulouse, INRA, INPT, ENVT,GenPhySE, Castanet Tolosan, France
[30] Univ Toronto, Dept Comp Sci, Toronto, ON, Canada
基金
美国国家卫生研究院; 俄罗斯科学基金会; 澳大利亚研究理事会; 英国生物技术与生命科学研究理事会;
关键词
GENOME-WIDE ASSOCIATION; GENE-EXPRESSION; TRANSCRIPTION; ARCHITECTURE; ANNOTATION; LANDSCAPE; EVOLUTION; DATABASE; LNCRNA; QUANTIFICATION;
D O I
10.1038/nature21374
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:199 / +
页数:19
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