The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
An integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072
Self-citationMapping and quantifying mammalian transcriptomes by RNA-Seq
Mortazavi, A., Williams, B. A., McCue, K., Schaeffer, L., & Wold, B. (2008) · Nature Methods · doi:10.1038/nmeth.1226 · Cited by 13,696
Self-citationThe ENCODE Project Consortium (2007) · Nature · doi:10.1038/nature05874 · Cited by 5,223
Self-citationGENCODE: The reference human genome annotation for The ENCODE Project
Harrow, J., Frankish, A., Gonzalez, J. M., Tapanari, E., Diekhans, M., Kokocinski, F., Aken, B. L., Barrell, D., Zadissa, A., Searle, S., et al. (2012) · Genome Research · doi:10.1101/gr.135350.111 · Cited by 4,585
Self-citationThe accessible chromatin landscape of the human genome
Thurman, R. E., Rynes, E., Humbert, R., Vierstra, J., Maurano, M. T., Haugen, E., Sheffield, N. C., Stergachis, A. B., Wang, H., Vernot, B., et al. (2012) · Nature · doi:10.1038/nature11232 · Cited by 2,679
Self-citationRNA Maps Reveal New RNA Classes and a Possible Function for Pervasive Transcription
Kapranov, P., Cheng, J., Dike, S., Nix, D. A., Duttagupta, R., Willingham, A. T., Stadler, P. F., Jana Hertel, A., Jörg Hackermüller, A., Hofacker, I. L., et al. (2007) · Science · doi:10.1126/science.1138341 · Cited by 2,519
Self-citationWidespread transcription at neuronal activity-regulated enhancers
Kim, T.-K., Hemberg, M., Gray, J. M., Costa, A. M., Bear, D. M., Wu, J., Harmin, D. A., Laptewicz, M., Barbara-Haley, K., Kuersten, S., et al. (2010) · Nature · doi:10.1038/nature09033 · Cited by 2,450
The ENCODE (ENCyclopedia Of DNA Elements) Project
(2004) · Science · doi:10.1126/science.1105136 · Cited by 2,390
Architecture of the human regulatory network derived from ENCODE data
Gerstein, M., Kundaje, A. B., Hariharan, M., Landt, S. G., Yan, K., Cheng, C., Mu, X. J., Khurana, E., Rozowsky, J. S., Alexander, R. P., et al. (2012) · Nature · doi:10.1038/nature11245 · Cited by 1,449
Self-citationTranscriptional Maps of 10 Human Chromosomes at 5-Nucleotide Resolution
Cheng, J., Kapranov, P., Drenkow, J., Dike, S., Brubaker, S., Patel, S. A., Long, J. C., Stern, D., Tammana, H., Helt, G. A., et al. (2005) · Science · doi:10.1126/science.1108625 · Cited by 1,192
Self-citation
Flagged first, then by citations
Research works printed but not linked: 2
- Tilgner, H. et al. Genomic analysis of ENCODE data reveals widespread links between epigenetic chromatin marks and alternative splicing. Genome Res. (in the press)
- Miller, B. Pre-programming of chromatin structure across the cell cycle. Genome Res. (in the press)
Cited by
Sorted by citations
Items 1,001–1,018 of 1,018
Decoding neuroproteomics: integrating the genome, translatome and functional anatomy
Kitchen, R. R., Rozowsky, J. S., Gerstein, M. B., & Nairn, A. C. (2014) · Nature Neuroscience · doi:10.1038/nn.3829 · Cited by 63
Self-citationChen, H., Du, G., Song, X., & Li, L. (2017) · Genomics, Proteomics & Bioinformatics · doi:10.1016/j.gpb.2017.02.003 · Cited by 85
Long‐noncoding RNA Atrolnc‐1 promotes muscle wasting in mice with chronic kidney disease
Sun, L., Si, M., Liu, X., Choi, J. M., Wang, Y., Thomas, S. S., Peng, H., & Hu, Z. (2018) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12321 · Cited by 60
Epigenetic Alteration in Colorectal Cancer: Potential Diagnostic and Prognostic Implications
Cao, Q., Tian, Y., Deng, Z., Yang, F., & Chen, E. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25063358 · Cited by 60
The lncRNA Toolkit: Databases and In Silico Tools for lncRNA Analysis
Pinkney, H. R., Wright, B. M., & Diermeier, S. D. (2020) · Non-Coding RNA · doi:10.3390/ncrna6040049 · Cited by 56
MicroRNAs, Long Non-Coding RNAs, and Circular RNAs in the Redox Control of Cell Senescence
Lettieri-Barbato, D., Aquilano, K., Punziano, C., Minopoli, G., & Faraonio, R. (2022) · Antioxidants · doi:10.3390/antiox11030480 · Cited by 51
RNA-Seq Reveals Novel Transcriptional Reorganization in Human Alcoholic Brain
Farris, S. P., & Dayne Mayfield, R. (2014) · International Review of Neurobiology · doi:10.1016/b978-0-12-801105-8.00011-4 · Cited by 49
Exploring Human-Genome Gut-Microbiome Interaction in Parkinson’s Disease
Wallen, Z. D., Stone, W. J., Factor, S. A., Molho, E., Zabetian, C. P., Standaert, D. G., & Payami, H. (2021) · npj Parkinson s Disease · doi:10.1038/s41531-021-00218-2 · Cited by 41
Noncoding RNA: from dark matter to bright star
Xue, Y., Chen, R., Qu, L., & Cao, X. (2020) · Science China Life Sciences · doi:10.1007/s11427-020-1676-5 · Cited by 38
Breast Cancer and the Other Non-Coding RNAs
Dvorská, D., Braný, D., Ňachajová, M., Halašová, E., & Danková, Z. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22063280 · Cited by 38
Gstir, R., Schafferer, S., Scheideler, M., Misslinger, M., Griehl, M., Daschil, N., Humpel, C., Obermair, G. J., Schmuckermair, C., Striessnig, J., et al. (2014) · RNA · doi:10.1261/rna.047225.114 · Cited by 36
Dluzen, D. F., Noren Hooten, N., & Evans, M. K. (2017) · WIREs RNA · doi:10.1002/wrna.1385 · Cited by 31
Exploring the read-write genome: mobile DNA and mammalian adaptation
Shapiro, J. A. (2017) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2016.1226748 · Cited by 30
Multi‐omics analysis reveals the functional transcription and potential translation of enhancers
Wu, Y., Yang, Y., Gu, H., Tao, B., Zhang, E., Wei, J., Wang, Z., Liu, A., Sun, R., Chen, M., et al. (2020) · International Journal of Cancer · doi:10.1002/ijc.33132 · Cited by 18
The role of enhancer RNAs in epigenetic regulation of gene expression
Rahnamoun, H., Orozco, P., & Lauberth, S. M. (2020) · Transcription · doi:10.1080/21541264.2019.1698934 · Cited by 16
Łabędzka-Dmoch, K., Kolondra, A., Karpińska, M. A., Dębek, S., Grochowska, J., Grochowski, M., Piątkowski, J., Hoang Diu Bui, T., & Golik, P. (2021) · RNA Biology · doi:10.1080/15476286.2021.1943929 · Cited by 8
Human iPSC Models in Drug Discovery: Opportunities and Challenges
Silva, M. C., Cross, A., Brandon, N. J., & Haggarty, S. J. (2017) · Comprehensive Medicinal Chemistry III · doi:10.1016/b978-0-12-409547-2.12284-x · Cited by 6
New generation of clinical epigenetics analysis and diagnosis for precision medicine
Song, P., & Li, B. (2025) · Diagnostics · doi:10.3390/diagnostics15121539 · Cited by 4
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
