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      Landscape of transcription in human cells

      1 , 2 , 1 , 2 , 7 , 5 , 8 , 1 , 1 , 2 , 2 , 2 , 5 , 4 , 5 , 2 , 13 , 14 , 1 , 12 , 7 , 1 , 5 , 2 , 17 , 2 , 2 , 3 , 2 , 11 , 10 , 1 , 1 , 2 , 3 , 3 , 3 , 9 , 2 , 2 , 1 , 3 , 6 , 3 , 1 , 2 , 11 , 10 , 2 , 1 , 3 , 16 , 5 , 1 , 6 , 8 , 2 , 2 , 1 , 4 , 9 , 1 , 5 , 2 , 6 , 1 , 17 , 7 , 7 , 1 , 5 , 10 , 2 , 4 , 11 , 6 , 7 , 12 , 13 , 14 , 15 , 12 , 10 , 9 , 2 , 4 , 11 , 6 , 5 , 7 , 1 , 2 , 3

      Nature

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Summary

          Eukaryotic cells make many types of primary and processed RNAs that are found either in specific sub-cellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic sub-cellular localizations are also poorly understood. Since 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, modifications 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 to a redefinition of the concept of a gene.

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          Most cited references 48

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          An Integrated Encyclopedia of DNA Elements in the Human Genome

          Summary The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure, and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall the project provides new insights into the organization and regulation of our genes and genome, and an expansive resource of functional annotations for biomedical research.
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            Mapping and quantifying mammalian transcriptomes by RNA-Seq.

            We have mapped and quantified mouse transcriptomes by deeply sequencing them and recording how frequently each gene is represented in the sequence sample (RNA-Seq). This provides a digital measure of the presence and prevalence of transcripts from known and previously unknown genes. We report reference measurements composed of 41-52 million mapped 25-base-pair reads for poly(A)-selected RNA from adult mouse brain, liver and skeletal muscle tissues. We used RNA standards to quantify transcript prevalence and to test the linear range of transcript detection, which spanned five orders of magnitude. Although >90% of uniquely mapped reads fell within known exons, the remaining data suggest new and revised gene models, including changed or additional promoters, exons and 3' untranscribed regions, as well as new candidate microRNA precursors. RNA splice events, which are not readily measured by standard gene expression microarray or serial analysis of gene expression methods, were detected directly by mapping splice-crossing sequence reads. We observed 1.45 x 10(5) distinct splices, and alternative splices were prominent, with 3,500 different genes expressing one or more alternate internal splices.
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              GENCODE: the reference human genome annotation for The ENCODE Project.

              The GENCODE Consortium aims to identify all gene features in the human genome using a combination of computational analysis, manual annotation, and experimental validation. Since the first public release of this annotation data set, few new protein-coding loci have been added, yet the number of alternative splicing transcripts annotated has steadily increased. The GENCODE 7 release contains 20,687 protein-coding and 9640 long noncoding RNA loci and has 33,977 coding transcripts not represented in UCSC genes and RefSeq. It also has the most comprehensive annotation of long noncoding RNA (lncRNA) loci publicly available with the predominant transcript form consisting of two exons. We have examined the completeness of the transcript annotation and found that 35% of transcriptional start sites are supported by CAGE clusters and 62% of protein-coding genes have annotated polyA sites. Over one-third of GENCODE protein-coding genes are supported by peptide hits derived from mass spectrometry spectra submitted to Peptide Atlas. New models derived from the Illumina Body Map 2.0 RNA-seq data identify 3689 new loci not currently in GENCODE, of which 3127 consist of two exon models indicating that they are possibly unannotated long noncoding loci. GENCODE 7 is publicly available from gencodegenes.org and via the Ensembl and UCSC Genome Browsers.
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                Author and article information

                Journal
                0410462
                6011
                Nature
                Nature
                Nature
                0028-0836
                1476-4687
                6 June 2013
                6 September 2012
                17 June 2013
                : 489
                : 7414
                : 101-108
                Affiliations
                [1 ]Centre for Genomic Regulation (CRG) and UPF, Doctor Aiguader, 88 . Barcelona, Catalunya, Spain 08003.
                [2 ]Cold Spring Harbor Laboratory, Functional Genomics, 1 Bungtown Rd. Cold Spring Harbor, NY, USA 11742.
                [3 ]Affymetrix, Inc, 3380 Central Expressway, Santa Clara, CA. USA 95051.
                [4 ]Boise State University, College of Arts & Sciences, 1910 University Dr. Boise, ID USA 83725.
                [5 ]California Institute of Technology, Division of Biology, 91125. 2 Beckman Institute, Pasadena, CA USA 91125.
                [6 ]Genome Institute of Singapore, Genome Technology and Biology, 60 Biopolis Street, #02-01, Genome, Singapore, Singapore 138672.
                [7 ]RIKEN Yokohama Institute, RIKEN Omics Science Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa Japan 230-0045.
                [8 ]University of California Irvine, Dept of. Developmental and Cell Biology, 2300 Biological Sciences III, Irving, CA USA 92697.
                [9 ]University of Geneva Medical School, Department of Genetic Medicine and Development and iGE3 Institute of Genetics and Genomics of Geneva, 1 rue Michel-Servet, Geneva, Switzerland 1015.
                [10 ]University of Lausanne, Center for Integrative Genomics, Genopode building, Lausanne, Switzerland 1015.
                [11 ]University of North Carolina at Chapel Hill, Department of Biochemistry & Biophysics, 120 Mason Farm Rd., Chapel Hill, NC USA 27599.
                [12 ]Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire United Kingdom CB10 1SA.
                [13 ]Program in Computational Biology and Bioinformatics, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520.
                [14 ]Department of Molecular Biophysics and Biochemistry, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520.
                [15 ]Department of Computer Science, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520.
                [16 ]St. Laurent Institute, One Kendall Square, Cambridge, MA.
                [17 ]Department of Chemical Engineering, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
                Author notes
                Corresponding Authors: - Thomas R. Gingeras, Cold Spring Harbor Laboratory. gingeras@ 123456cshl.edu - Roderic Guigó, Centre for Genomic Regulation. roderic.guigo@ 123456crg.eu
                [*]

                These authors contributed equally to this work

                Article
                NIHMS377835
                10.1038/nature11233
                3684276
                22955620

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                Funding
                Funded by: National Human Genome Research Institute : NHGRI
                Award ID: U54 HG007004 || HG
                Funded by: National Human Genome Research Institute : NHGRI
                Award ID: U54 HG004557 || HG
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