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Landscape of transcription in human cells
Open accessAbstract
Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell’s regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene. A description is given of the ENCODE effort to provide a complete catalogue of primary and processed RNAs found either in specific subcellular compartments or throughout the cell, revealing that three-quarters of the human genome can be transcribed, and providing a wealth of information on the range and levels of expression, localization, processing fates and modifications of known and previously unannotated RNAs. These authors describe the ENCODE (Encyclopedia of DNA Elements) effort to provide a complete catalogue of primary and processed RNAs found either in specific sub-cellular compartments or throughout the cell. They show that three-quarters of the human genome can be transcribed, and provide a wealth of information about the range and levels of expression, localization, processing fates and modifications of both known and previously unannotated RNAs. Collectively, these observations suggest that the current concept of a gene should be revisited.
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“Almost all human multi-exon genes exhibit alternative splicing, and spliced human genes have on average over nine alternative transcribed forms.”
From A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequencing Quality Control Consortium (2014) · cites this paper as [7]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The human genome now has >55,000 well-validated genes, and the majority of them are not protein coding.”
From A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequencing Quality Control Consortium (2014) · cites this paper as [7]
Experimental — accuracy not yet measuredIn the citing paper
“Efforts including ENCODE71 and others91, have reported that more than 75% of genomic DNA is at some point transcribed to primary (un-spliced) RNA.”
From Decoding neuroproteomics: integrating the genome, translatome and functional anatomy (2014) · cites this paper as [71]
In the citing paper
“A recent result that has a potentially significant impact on interpretation of proteomic data is the finding that most genes, in a given cell-type, likely express only a single ‘dominant’ transcript70,71.”
From Decoding neuroproteomics: integrating the genome, translatome and functional anatomy (2014) · cites this paper as [71]
In the citing paper
“RNA deep-sequencing (RNA-seq) provides a powerful tool to decipher global gene expression patterns far beyond the limitations of microarrays, including an unprecedented capability to discover novel genes, alternative transcript variants, chimeric transcripts, and expressed sequence variants as well as allele-specific expression [8–12].”
From Comparison of RNA-seq and microarray-based models for clinical endpoint prediction (2015) · cites this paper as [9]
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Metadata
- Authors
- Djebali, S., Davis, C. A., Merkel, A., Dobin, A., Lassmann, T., Mortazavi, A., Tanzer, A., Lagarde, J., Lin, W., Schlesinger, F., Xue, C., Marinov, G. K., Khatun, J., Williams, B. A., Zaleski, C., Rozowsky, J., Röder, M., Kokocinski, F., Abdelhamid, R. F., Alioto, T., Antoshechkin, I., Baer, M. T., Bar, N. S., Batut, P., Bell, K., Bell, I., Chakrabortty, S., Chen, X., Chrast, J., Curado, J., Derrien, T., Drenkow, J., Dumais, E., Dumais, J., Duttagupta, R., Falconnet, E., Fastuca, M., Fejes-Toth, K., Ferreira, P., Foissac, S., Fullwood, M. J., Gao, H., Gonzalez, D., Gordon, A., Gunawardena, H., Howald, C., Jha, S., Johnson, R., Kapranov, P., King, B., Kingswood, C., Luo, O. J., Park, E., Persaud, K., Preall, J. B., Ribeca, P., Risk, B., Robyr, D., Sammeth, M., Schaffer, L., See, L.-H., Shahab, A., Skancke, J., Suzuki, A. M., Takahashi, H., Tilgner, H., Trout, D., Walters, N., Wang, H., Wrobel, J., Yu, Y., Ruan, X., Hayashizaki, Y., Harrow, J., Gerstein, M., Hubbard, T., Reymond, A., Antonarakis, S. E., Hannon, G., Giddings, M. C., Ruan, Y., Wold, B., Carninci, P., Guigó, R., & Gingeras, T. R.
- Affiliations
- Centre for Genomic Regulation (ES)
- Universitat Pompeu Fabra (ES)
- Cold Spring Harbor Laboratory (US)
- California Institute of Technology (US)
- Boise State University (US)
- Wellcome Sanger Institute (GB)
- Norwegian University of Science and Technology (NO)
- University of North Carolina at Chapel Hill (US)
- University of Geneva (CH)
- Laboratoire de Génétique Cellulaire (FR)
- Corresponding author
- Guigó, Roderic
- Gingeras, Thomas R.
- ORCID
- Djebali, Sarah
- Merkel, Angelika
- Lassmann, Timo
- Mortazavi, Ali
- Lagarde, Julien
- Lin, Wei
- Marinov, Georgi K.
- Williams, Brian A.
- Rozowsky, Joel
- Kokocinski, Felix
- Abdelhamid, Rehab F.
- Alioto, Tyler
- Antoshechkin, Igor
- Bar, Nadav S.
- Batut, Philippe
- Bell, Kimberly
- Chen, Xian
- Derrien, Thomas
- Ferreira, Pedro
- Foissac, Sylvain
- Fullwood, Melissa J.
- Gao, Hui
- Gunawardena, Harsha
- Johnson, Rory
- Kapranov, Philipp
- Luo, Oscar J.
- Park, Eddie
- Preall, Jonathan B.
- Ribeca, Paolo
- Sammeth, Michael
- Shahab, Atif
- Takahashi, Hazuki
- Tilgner, Hagen
- Trout, Diane
- Wrobel, John
- Yu, Yanbao
- Hayashizaki, Yoshihide
- Harrow, Jennifer
- Gerstein, Mark
- Hubbard, Tim
- Reymond, Alexandre
- Antonarakis, Stylianos E.
- Hannon, Gregory
- Ruan, Yijun
- Wold, Barbara
- Carninci, Piero
- Guigó, Roderic
- Gingeras, Thomas R.
- Venue
- Nature
- Published
- 2012-09
- Volume
- 489
- Issue
- 7414
- Pages
- 101-108
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3684276
- OpenAlex
- W2166810745
- Cited by
- 5,187
- References
- 42
- Citations by year
- 2026: 102 · 2025: 217 · 2024: 347 · 2023: 332 · 2022: 372 · 2021: 487 · 2020: 523 · 2019: 421 · 2018: 440 · 2017: 429 · 2016: 392 · 2015: 357 · 2014: 389 · 2013: 323 · 2012: 49
- FWCI
- 143.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- SERVAL (Université de Lausanne) (acceptedVersion, other-oa)
- Archive ouverte UNIGE (University of Geneva) (acceptedVersion, other-oa)
- Scholar Works (Boise State University) (submittedVersion, cc-by-nc-sa)
- HAL (submittedVersion, other-oa)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-sa)
- IRIS (submittedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by-nc-sa)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Science Foundation
- Wellcome Trust (062023)
- Ministry of Education, Culture, Sports, Science and Technology
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (26205, 127375, 249968)
- National Institutes of Health (5u54hg004555-04, 5p30ca045508-35)
- RIKEN
- National Human Genome Research Institute (U54HG007004, R01HG003700, U54HG004576, U54-HG004555, U54HG004558, U01HG003147, RC2HG005591, U54HG004557, U24HG007234)
- National Cancer Institute (P30-CA045508)
- National Institute of General Medical Sciences (R37GM062534)
- FP7 Ideas: European Research Council (249968)
- Topics
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- transcription, human genome, RNA processing, RNA localization, RNA modification, gene definition, ENCODE, RNA expression levels, genome annotation
- MeSH terms
- Alleles, Cell Line, DNA, Encyclopedias as Topic, Enhancer Elements, Genetic, Exons, Genes, Humans, Regulatory Sequences, Nucleic Acid, Repetitive Sequences, Nucleic Acid, RNA, RNA Splicing, Transcription, Genetic, Genome, Human, RNA Editing, Sequence Analysis, RNA, Protein Isoforms, Gene Expression Profiling, DNA, Intergenic, Genomics, Polyadenylation, Molecular Sequence Annotation, Transcriptome
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