1. Evidence for Transcript Networks Composed of Chimeric RNAs in Human Cells
- Author
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Vincent Lacroix, Sylvain Foissac, Ryan R. Murray, Sarah Djebali, Cédric Howald, Josep Lluís Gelpí, Paolo Ribeca, Alexandre Reymond, Kourosh Salehi-Ashtiani, Marc Vidal, Roderic Guigó, Thomas R. Gingeras, John A. Stamatoyannopoulos, Erica Dumais, Alexander Dobin, Bryan R. Lajoie, Tim Hubbard, Stylianos E. Antonarakis, Catherine Ucla, Ian Bell, Jacqueline Chrast, Alfonso Valencia, Modesto Orozco, Philippe Batut, Christelle Borel, Adam Frankish, Philipp Kapranov, Jorg Drenkow, Michael L. Tress, Chenwei Lin, Jennifer Harrow, Xinping Yang, Lila Ghamsari, Job Dekker, David C. Martin, Jonathan M. Mudge, Julien Lagarde, Nynke L. van Berkum, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Universitat Pompeu Fabra [Barcelona] (UPF), Affymetrix Inc., Geneva University Hospital (HUG), The Wellcome Trust Sanger Institute [Cambridge], Laboratoire de Génétique Cellulaire (LGC), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université de Lausanne (UNIL), Dana-Farber Cancer Institute [Boston], Harvard University [Cambridge], Cold Spring Harbor Laboratory, Spanish National Cancer Research Centre, University of Barcelona, Sagot, Marie-France, Universitat de Barcelona, Centro de Regulación Genómica (CRG), Affymetrix, An algorithmic view on genomes, cells, and environments (BAMBOO), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université de Genève (UNIGE), Sanger Institute, Wellcome Trust, Harvard Medical School [Boston] (HMS), Cold Spring Harbor Laboratory (CSHL), Spanish National Cancer Research Center (CNIO), Universitat de Barcelona (UB), University of Massachusetts [Amherst] (UMass Amherst), University of Massachusetts System (UMASS), University of Washington [Seattle], Universitat Pompeu Fabra [Barcelona], Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Université de Lausanne = University of Lausanne (UNIL), Harvard University, Université de Genève = University of Geneva (UNIGE), Borel, Christelle, Ucla, Catherine, Martin, David, Reymond, Alexandre, and Antonarakis, Stylianos
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Male ,Transcription, Genetic ,Microarrays ,[SDV]Life Sciences [q-bio] ,Gene Identification and Analysis ,lcsh:Medicine ,Gene Expression ,Validation Studies as Topic ,Transcriptomes ,Exon ,Transcriptome/physiology ,0302 clinical medicine ,Transcripció genètica ,Gene Regulatory Networks/genetics/physiology ,RNA Isoforms ,Gene expression ,Molecular Cell Biology ,site ,ddc:576.5 ,Cells/metabolism ,Gene Regulatory Networks ,Molecular genetics ,Nucleic Acid Amplification Techniques/methods ,lcsh:Science ,[INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM] ,Genetics ,0303 health sciences ,Multidisciplinary ,[SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,Genetic transcription ,element ,Statistics ,[SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN] ,tool ,Genomics ,reverse transcription ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,3. Good health ,encode ,Chromosomes, Human, Pair 1/genetics ,annotation ,Chromosomes, Human, Pair 1 ,RNA/genetics/physiology ,[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Female ,Sequence Analysis ,Nucleic Acid Amplification Techniques ,Algorithms ,Research Article ,[SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT] ,Cells ,cloning ,Chimerin Proteins/chemistry/genetics ,Chimeric gene ,Biology ,Metabolisme cel·lular ,Biostatistics ,Models, Biological ,Genètica molecular ,Molecular Genetics ,03 medical and health sciences ,Genome Analysis Tools ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,human genome ,Chimerin Proteins/chemistry ,Chimerin Proteins/genetics ,Gene Expression Profiling ,Gene Regulatory Networks/genetics ,Gene Regulatory Networks/physiology ,Humans ,Microarray Analysis/methods ,RNA/genetics ,RNA/physiology ,RNA Isoforms/chemistry ,RNA Isoforms/genetics ,Transcription, Genetic/genetics ,Gene ,030304 developmental biology ,RNA Isoforms/chemistry/genetics/metabolism ,[SDV.OT] Life Sciences [q-bio]/Other [q-bio.OT] ,lcsh:R ,Chimerin Proteins ,RNA ,gene fusion ,Computational Biology ,Microarray Analysis ,Gene expression profiling ,[SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN] ,Human genome ,lcsh:Q ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,discovery ,Genome Expression Analysis ,Transcriptome ,030217 neurology & neurosurgery ,Genètica ,Mathematics - Abstract
The classic organization of a gene structure has followed the Jacob and Monod bacterial gene model proposed more than 50 years ago. Since then, empirical determinations of the complexity of the transcriptomes found in yeast to human has blurred the definition and physical boundaries of genes. Using multiple analysis approaches we have characterized individual gene boundaries mapping on human chromosomes 21 and 22. Analyses of the locations of the 5' and 3' transcriptional termini of 492 protein coding genes revealed that for 85% of these genes the boundaries extend beyond the current annotated termini, most often connecting with exons of transcripts from other well annotated genes. The biological and evolutionary importance of these chimeric transcripts is underscored by (1) the non-random interconnections of genes involved, (2) the greater phylogenetic depth of the genes involved in many chimeric interactions, (3) the coordination of the expression of connected genes and (4) the close in vivo and three dimensional proximity of the genomic regions being transcribed and contributing to parts of the chimeric RNAs. The non-random nature of the connection of the genes involved suggest that chimeric transcripts should not be studied in isolation, but together, as an RNA network. This work has been supported by grants U01HG003150 and U01HG003147 from the National Human Genome Research for the ENCODE project. RG was also supported by a grant from the Spanish Ministry of Education and Science. In addition, KS-A, RM, XY, CL, LG and MV were supported by a grant from the Ellison Foundation and as Institute Sponsored Research from the Dana Farber Cancer Institute Strategic Initiative. The laboratories of SA and AR were supported by grants from the Swiss National Science Foundation and the European Commission AnEUploidy Integrated Project. SA was also supported by the National Center of Excellence ‘‘Frontiers in Genetics’’, ChildCare Foundation and an ERC grant from the European Union. AF, TH and JM acknowledge support from the Wellcome Trust. The work of JLG and MO has been supported by the Spanish Ministry of Science (CTQ2005-09365-C02-02, BIO2009-10964), Instituto Nacional de Bioinformática, the Consolider E-science project (CSD2007-00050), COMBIOMED RETICS and the Fundación Marcelino Botin. JD is supported by a grant from the National Institutes of Health (HG003143) and a W. M. Keck Foundation Distinguished Young Scholar Award. JS is supported by a grant from the National Institutes of Health (U54 HG004592). The work of MT and AV was supported by Consolider E-Science (CSD2007-00050) and the Instituto Nacional de Bioinformática. MV (Center for Cancer Systems Biology, CCSB) is a ‘‘Chercheur Qualifié Honoraire’’ from the Fonds de la Recherche Scientifique (FRS-FNRS, French Community of Belgium). This work has also been funded by grant to TG by NHGRI (U54HG004557) and partially byAffymetirix, Corp
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- 2012