An atlas of human long non-coding RNAs with accurate 5′ ends
Open accessAbstract
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.
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A majority of novel TSSs were supported by spliced transcripts from RNA-seq and expressed sequence tags.
“A majority of the novel TSSs were supported by spliced transcripts (see methods) from RNA-seq25,26 and expressed sequence tag27”
From Alternative promoters in CpG depleted regions are prevalently associated with epigenetic misregulation of liver cancer transcriptomes (2023) · cites this paper as [25]
The ‘Building a 5′ complete transcriptome’ section describes identifying TSSs using transcript models, including an RNA-seq assembly, and considers transcript exon number. The Methods section on FANTOM5 RNA-seq also describes assembling splice junctions. Neither passage establishes that a majority of novel TSSs were supported by spliced transcripts or identifies expressed sequence tags as support. (LLM, conf=0.76)
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- Authors
- Hon, C.-C., Ramilowski, J. A., Harshbarger, J., Bertin, N., Rackham, O. J. L., Gough, J., Denisenko, E., Schmeier, S., Poulsen, T. M., Severin, J., Lizio, M., Kawaji, H., Kasukawa, T., Itoh, M., Burroughs, A. M., Noma, S., Djebali, S., Alam, T., Medvedeva, Y. A., Testa, A. C., Lipovich, L., Yip, C.-W., Abugessaisa, I., Mendez, M., Hasegawa, A., Tang, D., Lassmann, T., Heutink, P., Babina, M., Wells, C. A., Kojima, S., Nakamura, Y., Suzuki, H., Daub, C. O., de Hoon, M. J. L., Arner, E., Hayashizaki, Y., Carninci, P., & Forrest, A. R. R.
- Affiliations
- RIKEN (JP)
- National University of Singapore (SG)
- University of Bristol (GB)
- Massey University (NZ)
- National Institute of Advanced Industrial Science and Technology (JP)
- National Institutes of Health (US)
- Universitat Pompeu Fabra (ES)
- King Abdullah University of Science and Technology (SA)
- Russian Academy of Sciences (RU)
- The University of Western Australia (AU)
- Wayne State University (US)
- The Kids Research Institute Australia (AU)
- German Center for Neurodegenerative Diseases (DE)
- Charité – Universitätsmedizin Berlin (DE)
- The University of Queensland (AU)
- University of Tsukuba (JP)
- Karolinska Institutet (SE)
- Corresponding author
- Carninci, Piero
- Forrest, Alistair R. R.
- ORCID
- Hon, Chung-Chau
- Ramilowski, Jordan A.
- Harshbarger, Jayson
- Bertin, Nicolas
- Rackham, Owen J. L.
- Gough, Julian
- Denisenko, Elena
- Schmeier, Sebastian
- Severin, Jessica
- Lizio, Marina
- Kawaji, Hideya
- Kasukawa, Takeya
- Itoh, Masayoshi
- Burroughs, A. Maxwell
- Noma, Shohei
- Djebali, Sarah
- Alam, Tanvir
- Medvedeva, Yulia A.
- Lipovich, Leonard
- Abugessaisa, Imad
- Mendez, Mickaël
- Hasegawa, Akira
- Tang, Dave
- Lassmann, Timo
- Heutink, Peter
- Babina, Magda
- Wells, Christine A.
- Kojima, Soichi
- Nakamura, Yukio
- Suzuki, Harukazu
- Daub, Carsten O.
- Hayashizaki, Yoshihide
- Carninci, Piero
- Forrest, Alistair R. R.
- Venue
- Nature
- Published
- 2017-03
- Volume
- 543
- Issue
- 7644
- Pages
- 199-204
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6857182
- OpenAlex
- W2593488635
- Cited by
- 1,007
- References
- 13
- Citations by year
- 2026: 38 · 2025: 52 · 2024: 70 · 2023: 95 · 2022: 103 · 2021: 160 · 2020: 167 · 2019: 126 · 2018: 117 · 2017: 78
- FWCI
- 45.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- UWA Profiles and Research Repository (UWA) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- DZNE Pub (submittedVersion)
- King Abdullah University of Science and Technology Repository (King Abdullah University of Science and Technology) (submittedVersion)
- Funders
- Conquer Cancer Foundation
- Ministry of Education, Culture, Sports, Science and Technology
- Ministerio de Economía y Competitividad (SEV‐2012‐0208, BIO2011-26205)
- Russian Science Foundation (15-14-30002)
- National Institutes of Health
- Biotechnology and Biological Sciences Research Council (BB/G022771/1)
- Australian Research Council (DP160101960)
- RIKEN
- National Human Genome Research Institute (U54HG007004)
- National Cancer Institute (DP2CA196375, P30CA022453)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- long non-coding RNA, CAGE, lncRNA expression profiles, intergenic lncRNAs, single nucleotide polymorphisms, expression quantitative trait loci, transcriptional regulation, lncRNA conservation, tissue expression
- MeSH terms
- Cells, Cultured, Enhancer Elements, Genetic, Gene Expression Regulation, Humans, Organ Specificity, Promoter Regions, Genetic, RNA, Messenger, Genome, Human, Conserved Sequence, Internet, Polymorphism, Single Nucleotide, Gene Expression Profiling, RNA Stability, Genomics, Databases, Genetic, Quantitative Trait Loci, Epigenesis, Genetic, Genome-Wide Association Study, Molecular Sequence Annotation, Transcriptome, RNA, Long Noncoding, Datasets as Topic
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