This Article Full Text Full Text (PDF) Supplemental Research Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kapranov, P. Articles by Gingeras, T. R. Search for Related Content PubMed PubMed Citation Articles by Kapranov, P. Articles by Gingeras, T. R. Social Bookmarking                   What's this?

Methods

Examples of the complex architecture of the human transcriptome revealed by RACE and high-density tiling arrays

Affymetrix Inc., Santa Clara, California 95051, USA

Recently, we mapped the sites of transcription across 30% of the human genome and elucidated the structures of several hundred novel transcripts. In this report, we describe a novel combination of techniques including the rapid amplification of cDNA ends (RACE) and tiling array technologies that was used to further characterize transcripts in the human transcriptome. This technical approach allows for several important pieces of information to be gathered about each array-detected transcribed region, including strand of origin, start and termination positions, and the exonic structures of spliced and unspliced coding and noncoding RNAs. In this report, the structures of transcripts from 14 transcribed loci, representing both known genes and unannotated transcripts taken from the several hundred randomly selected unannotated transcripts described in our previous work are represented as examples of the complex organization of the human transcriptome. As a consequence of this complexity, it is not unusual that a single base pair can be part of an intricate network of multiple isoforms of overlapping sense and antisense transcripts, the majority of which are unannotated. Some of these transcripts follow the canonical splicing rules, whereas others combine the exons of different genes or represent other types of noncanonical transcripts. These results have important implications concerning the correlation of genotypes to phenotypes, the regulation of complex interlaced transcriptional patterns, and the definition of a gene.

¹ Corresponding author.
E-mail philipp_kapranov{at}affymetrix.com; fax (408) 481-0422.

[Supplemental material is available online at www.genome.org. Sequences of RT-PCR products reported in this manuscript were deposited in GenBank under accession nos. AY927416-AY927467.]

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				O. Martinez and M. H. Reyes-Valdes Defining diversity, specialization, and gene specificity in transcriptomes through information theory PNAS, July 15, 2008; 105(28): 9709 - 9714. [Abstract] [Full Text] [PDF]

				G. Di Segni, S. Gastaldi, and G. P. Tocchini-Valentini From the Cover: Cis- and trans-splicing of mRNAs mediated by tRNA sequences in eukaryotic cells PNAS, May 13, 2008; 105(19): 6864 - 6869. [Abstract] [Full Text] [PDF]

				M. Huvet, S. Nicolay, M. Touchon, B. Audit, Y. d'Aubenton-Carafa, A. Arneodo, and C. Thermes Human gene organization driven by the coordination of replication and transcription Genome Res., September 1, 2007; 17(9): 1278 - 1285. [Abstract] [Full Text] [PDF]

				M. F. Mehler and J. S. Mattick Noncoding RNAs and RNA Editing in Brain Development, Functional Diversification, and Neurological Disease Physiol Rev, July 1, 2007; 87(3): 799 - 823. [Abstract] [Full Text] [PDF]

				K. Tsuritani, T. Irie, R. Yamashita, Y. Sakakibara, H. Wakaguri, A. Kanai, J. Mizushima-Sugano, S. Sugano, K. Nakai, and Y. Suzuki Distinct class of putative "non-conserved" promoters in humans: Comparative studies of alternative promoters of human and mouse genes Genome Res., July 1, 2007; 17(7): 1005 - 1014. [Abstract] [Full Text] [PDF]

				T. R. Gingeras Origin of phenotypes: Genes and transcripts Genome Res., June 1, 2007; 17(6): 682 - 690. [Abstract] [Full Text] [PDF]

				F. Denoeud, P. Kapranov, C. Ucla, A. Frankish, R. Castelo, J. Drenkow, J. Lagarde, T. Alioto, C. Manzano, J. Chrast, et al. Prominent use of distal 5' transcription start sites and discovery of a large number of additional exons in ENCODE regions Genome Res., June 1, 2007; 17(6): 746 - 759. [Abstract] [Full Text] [PDF]

				J. M. Lin, P. J. Collins, N. D. Trinklein, Y. Fu, H. Xi, R. M. Myers, and Z. Weng Transcription factor binding and modified histones in human bidirectional promoters Genome Res., June 1, 2007; 17(6): 818 - 827. [Abstract] [Full Text] [PDF]

				Y. Ruan, H. S. Ooi, S. W. Choo, K. P. Chiu, X. D. Zhao, K.G. Srinivasan, F. Yao, C. Y. Choo, J. Liu, P. Ariyaratne, et al. Fusion transcripts and transcribed retrotransposed loci discovered through comprehensive transcriptome analysis using Paired-End diTags (PETs) Genome Res., June 1, 2007; 17(6): 828 - 838. [Abstract] [Full Text] [PDF]

				D. Zheng, A. Frankish, R. Baertsch, P. Kapranov, A. Reymond, S. W. Choo, Y. Lu, F. Denoeud, S. E. Antonarakis, M. Snyder, et al. Pseudogenes in the ENCODE regions: Consensus annotation, analysis of transcription, and evolution Genome Res., June 1, 2007; 17(6): 839 - 851. [Abstract] [Full Text] [PDF]

				S. Washietl, J. S. Pedersen, J. O. Korbel, C. Stocsits, A. R. Gruber, J. Hackermuller, J. Hertel, M. Lindemeyer, K. Reiche, A. Tanzer, et al. Structured RNAs in the ENCODE selected regions of the human genome Genome Res., June 1, 2007; 17(6): 852 - 864. [Abstract] [Full Text] [PDF]

				J. S. Mattick A new paradigm for developmental biology J. Exp. Biol., May 1, 2007; 210(9): 1526 - 1547. [Abstract] [Full Text] [PDF]

				A. Werner, G. Schmutzler, M. Carlile, C. G. Miles, and H. Peters Expression profiling of antisense transcripts on DNA arrays Physiol Genomics, February 12, 2007; 28(3): 294 - 300. [Abstract] [Full Text] [PDF]

				K. V. Prasanth and D. L. Spector Eukaryotic regulatory RNAs: an answer to the 'genome complexity' conundrum Genes & Dev., January 1, 2007; 21(1): 11 - 42. [Abstract] [Full Text] [PDF]

				D. Miller and G.C. Ostermeier Towards a better understanding of RNA carriage by ejaculate spermatozoa Hum. Reprod. Update, November 1, 2006; 12(6): 757 - 767. [Abstract] [Full Text] [PDF]

				M. F. Mehler and J. S. Mattick Non-coding RNAs in the nervous system J. Physiol., September 1, 2006; 575(2): 333 - 341. [Abstract] [Full Text] [PDF]

				S. Gustincich, A. Sandelin, C. Plessy, S. Katayama, R. Simone, D. Lazarevic, Y. Hayashizaki, and P. Carninci The complexity of the mammalian transcriptome J. Physiol., September 1, 2006; 575(2): 321 - 332. [Abstract] [Full Text] [PDF]

				M. Sun, L. D. Hurst, G. G. Carmichael, and J. Chen Evidence for variation in abundance of antisense transcripts between multicellular animals but no relationship between antisense transcription and organismic complexity Genome Res., July 1, 2006; 16(7): 922 - 933. [Abstract] [Full Text] [PDF]

				J. S. Mattick and I. V. Makunin Non-coding RNA. Hum. Mol. Genet., April 15, 2006; 15(suppl_1): R17 - R29. [Abstract] [Full Text] [PDF]

				L. David, W. Huber, M. Granovskaia, J. Toedling, C. J. Palm, L. Bofkin, T. Jones, R. W. Davis, and L. M. Steinmetz A high-resolution map of transcription in the yeast genome PNAS, April 4, 2006; 103(14): 5320 - 5325. [Abstract] [Full Text] [PDF]

				T. R. Gingeras Transcripts of unknown function in eukaryotic cells: Lessons forgotten and re-learned. AACR Meeting Abstracts, April 1, 2006; 2006(1): 1355 - 1356. [Abstract]

				N. Vinckenbosch, I. Dupanloup, and H. Kaessmann Evolutionary fate of retroposed gene copies in the human genome PNAS, February 28, 2006; 103(9): 3220 - 3225. [Abstract] [Full Text] [PDF]

				A. Huttenhofer and J. Vogel Experimental approaches to identify non-coding RNAs Nucleic Acids Res., January 25, 2006; 34(2): 635 - 646. [Abstract] [Full Text] [PDF]

				K. Kimura, A. Wakamatsu, Y. Suzuki, T. Ota, T. Nishikawa, R. Yamashita, J.-i. Yamamoto, M. Sekine, K. Tsuritani, H. Wakaguri, et al. Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes Genome Res., January 1, 2006; 16(1): 55 - 65. [Abstract] [Full Text] [PDF]

				T. Ravasi, H. Suzuki, K. C. Pang, S. Katayama, M. Furuno, R. Okunishi, S. Fukuda, K. Ru, M. C. Frith, M. M. Gongora, et al. Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome Genome Res., January 1, 2006; 16(1): 11 - 19. [Abstract] [Full Text] [PDF]

				J. Cheong, Y. Yamada, R. Yamashita, T. Irie, A. Kanai, H. Wakaguri, K. Nakai, T. Ito, I. Saito, S. Sugano, et al. Diverse DNA Methylation Statuses at Alternative Promoters of Human Genes in Various Tissues DNA Res, January 1, 2006; 13(4): 155 - 167. [Abstract] [Full Text] [PDF]

				P. F.R. Little Structure and function of the human genome Genome Res., December 1, 2005; 15(12): 1759 - 1766. [Abstract] [Full Text] [PDF]

				M. R. Brent Genome annotation past, present, and future: How to define an ORF at each locus Genome Res., December 1, 2005; 15(12): 1777 - 1786. [Abstract] [Full Text] [PDF]

				J. S. Mattick The Functional Genomics of Noncoding RNA Science, September 2, 2005; 309(5740): 1527 - 1528. [Abstract] [Full Text] [PDF]