Evidence for transcript networks composed of chimeric RNAs in human cells

• Published in: PloS one Vol. 7; no. 1; p. e28213
• Main Authors: Djebali, Sarah, Lagarde, Julien, Kapranov, Philipp, Lacroix, Vincent, Borel, Christelle, Mudge, Jonathan M, Howald, Cédric, Foissac, Sylvain, Ucla, Catherine, Chrast, Jacqueline, Ribeca, Paolo, Martin, David, Murray, Ryan R, Yang, Xinping, Ghamsari, Lila, Lin, Chenwei, Bell, Ian, Dumais, Erica, Drenkow, Jorg, Tress, Michael L, Gelpí, Josep Lluís, Orozco, Modesto, Valencia, Alfonso, van Berkum, Nynke L, Lajoie, Bryan R, Vidal, Marc, Stamatoyannopoulos, John, Batut, Philippe, Dobin, Alex, Harrow, Jennifer, Hubbard, Tim, Dekker, Job, Frankish, Adam, Salehi-Ashtiani, Kourosh, Reymond, Alexandre, Antonarakis, Stylianos E, Guigó, Roderic, Gingeras, Thomas R
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 04-01-2012; Public Library of Science (PLoS)
• Subjects: Algorithms; Analysis; Annotations; Biochemistry; Biochemistry, Molecular Biology; Bioinformatics; Biological evolution; Biology; Boundaries; Cancer; Cells (Biology); Cells - metabolism; Chimerin Proteins - chemistry; Chimerin Proteins - genetics; Chromosomes; Chromosomes, Human, Pair 1 - genetics; Cloning; Computer Science; Empirical analysis; Encyclopedias; Exons; Female; Gene expression; Gene Expression Profiling; Gene mapping; Gene Regulatory Networks - genetics; Gene Regulatory Networks - physiology; Genes; Genetic aspects; Genetic transcription; Genetics; Genomes; Genomics; Genètica molecular; Humans; Laboratories; Life Sciences; Male; Mathematics; Medical research; Medical schools; Microarray Analysis - methods; Models, Biological; Molecular genetics; Molecular Networks; Nucleic Acid Amplification Techniques - methods; Other; Pharmacology; Phylogeny; Physicians; Proteomics; Quantitative Methods; Ribonucleic acid; RNA; RNA - genetics; RNA - physiology; RNA Isoforms - chemistry; RNA Isoforms - genetics; RNA Isoforms - metabolism; Supercomputers; Transcripció genètica; Transcription; Transcription (Genetics); Transcription, Genetic - genetics; Transcriptome - physiology; Validation Studies as Topic; Yeast; New York; United Kingdom > UK; United States > US; Massachusetts; California; Switzerland; Abu Dhabi United Arab Emirates; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0028213

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.