The complexity of the mammalian transcriptome

A comprehensive understanding of protein and regulatory networks is strictly dependent on the complete description of the transcriptome of cells. After the determination of the genome sequence of several mammalian species, gene identification is based on in silico predictions followed by evidence of transcription. Conservative estimates suggest that there are about 20 000 protein‐encoding genes in the mammalian genome. In the last few years the combination of full‐length cDNA cloning, cap‐analysis gene expression (CAGE) tag sequencing and tiling arrays experiments have unveiled unexpected additional complexities in the transcriptome. Here we describe the current view of the mammalian transcriptome focusing on transcripts diversity, the growing non‐coding RNA world, the organization of transcriptional units in the genome and promoter structures. In‐depth analysis of the brain transcriptome has been challenging due to the cellular complexity of this organ. Here we present a computational analysis of CAGE data from different regions of the central nervous system, suggesting distinctive mechanisms of brain‐specific transcription.

[1]  Terry Gaasterland,et al.  Impact of alternative initiation, splicing, and termination on the diversity of the mRNA transcripts encoded by the mouse transcriptome. , 2003, Genome research.

[2]  Jun Kawai,et al.  Differential Use of Signal Peptides and Membrane Domains Is a Common Occurrence in the Protein Output of Transcriptional Units , 2006, PLoS genetics.

[3]  J. Mattick,et al.  Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome. , 2005, Genome research.

[4]  J. Kawai,et al.  Cap analysis gene expression for high-throughput analysis of transcriptional starting point and identification of promoter usage , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[5]  J. Mattick Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms. , 2003, BioEssays : news and reviews in molecular, cellular and developmental biology.

[6]  Jun Kawai,et al.  Evolutionary turnover of mammalian transcription start sites. , 2006, Genome research.

[7]  Philipp Kapranov,et al.  Examples of the complex architecture of the human transcriptome revealed by RACE and high-density tiling arrays. , 2005, Genome research.

[8]  A. Berdal,et al.  Natural antisense transcripts: sound or silence? , 2005, Physiological Genomics.

[9]  Yoshihide Hayashizaki,et al.  Antisense transcripts with FANTOM2 clone set and their implications for gene regulation. , 2003, Genome research.

[10]  Boris Lenhard,et al.  Antisense Transcription in the Mammalian Transcriptome RIKEN Genome Exploration Research Group and Genome Science Group (Genome Network Project Core Group) and the FANTOM Consortium , 2005 .

[11]  Piero Carninci,et al.  Genome Network and FANTOM3: Assessing the Complexity of the Transcriptome , 2006, PLoS genetics.

[12]  Gabriel Kreiman,et al.  Gene expression changes and molecular pathways mediating activity-dependent plasticity in visual cortex , 2006, Nature Neuroscience.

[13]  Piero Carninci,et al.  Transcriptional network dynamics in macrophage activation. , 2006, Genomics.

[14]  Leah Barrera,et al.  A high-resolution map of active promoters in the human genome , 2005, Nature.

[15]  M. Fagiolini,et al.  Targeting a complex transcriptome: the construction of the mouse full-length cDNA encyclopedia. , 2003, Genome research.

[16]  John S Mattick,et al.  Non‐coding RNAs in the nervous system , 2006, The Journal of physiology.

[17]  R H Masland,et al.  Confronting complexity: strategies for understanding the microcircuitry of the retina. , 2000, Annual review of neuroscience.

[18]  The FANTOM Consortium and the RIKEN Genome Exploration Team,et al.  Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs , 2002 .

[19]  J. Mattick RNA regulation: a new genetics? , 2004, Nature Reviews Genetics.

[20]  Yoshihide Hayashizaki,et al.  Disclosing hidden transcripts: mouse natural sense-antisense transcripts tend to be poly(A) negative and nuclear localized. , 2005, Genome research.

[21]  Erez Y. Levanon,et al.  Widespread occurrence of antisense transcription in the human genome , 2003, Nature Biotechnology.

[22]  Sin Lam Tan,et al.  Complex Loci in Human and Mouse Genomes , 2006, PLoS genetics.

[23]  K. Kadota,et al.  Gene discovery in genetically labeled single dopaminergic neurons of the retina. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[24]  S. Salzberg,et al.  The Transcriptional Landscape of the Mammalian Genome , 2005, Science.

[25]  E. Schadt,et al.  Dark matter in the genome: evidence of widespread transcription detected by microarray tiling experiments. , 2005, Trends in genetics : TIG.

[26]  G. Helt,et al.  Transcriptional Maps of 10 Human Chromosomes at 5-Nucleotide Resolution , 2005, Science.

[27]  L. Hurst,et al.  Genome-wide analysis of coordinate expression and evolution of human cis-encoded sense-antisense transcripts. , 2005, Trends in genetics : TIG.

[28]  S. Nelson,et al.  Molecular taxonomy of major neuronal classes in the adult mouse forebrain , 2006, Nature Neuroscience.

[29]  J. Mattick,et al.  Rapid evolution of noncoding RNAs: lack of conservation does not mean lack of function. , 2006, Trends in genetics : TIG.

[30]  Ben Lehner,et al.  Antisense transcripts in the human genome. , 2002, Trends in genetics : TIG.

[31]  S. Batalov,et al.  Analysis of the mouse transcriptome for genes involved in the function of the nervous system. , 2003, Genome research.

[32]  Mouse Genome Sequencing Consortium Initial sequencing and comparative analysis of the mouse genome , 2002, Nature.

[33]  Sarah Barber,et al.  A mouse atlas of gene expression: large-scale digital gene-expression profiles from precisely defined developing C57BL/6J mouse tissues and cells. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[34]  S. Batalov,et al.  Antisense Transcription in the Mammalian Transcriptome , 2005, Science.

[35]  Piero Carninci,et al.  Tag-based approaches for transcriptome research and genome annotation , 2005, Nature Methods.

[36]  J. V. Moran,et al.  Initial sequencing and analysis of the human genome. , 2001, Nature.

[37]  C. Kai,et al.  CAGE: cap analysis of gene expression , 2006, Nature Methods.

[38]  International Human Genome Sequencing Consortium Initial sequencing and analysis of the human genome , 2001, Nature.

[39]  S. P. Fodor,et al.  Large-Scale Transcriptional Activity in Chromosomes 21 and 22 , 2002, Science.

[40]  J. Mattick The Functional Genomics of Noncoding RNA , 2005, Science.

[41]  J. Claverie,et al.  The significance of digital gene expression profiles. , 1997, Genome research.

[42]  Martin S. Taylor,et al.  Genome-wide analysis of mammalian promoter architecture and evolution , 2006, Nature Genetics.

[43]  T. Hughes,et al.  A systematic search for new mammalian noncoding RNAs indicates little conserved intergenic transcription , 2005, BMC Genomics.

[44]  Thomas E. Royce,et al.  Global Identification of Human Transcribed Sequences with Genome Tiling Arrays , 2004, Science.

[45]  S. Cawley,et al.  Novel RNAs identified from an in-depth analysis of the transcriptome of human chromosomes 21 and 22. , 2004, Genome research.

[46]  Xiaoqiu Huang,et al.  Over 20% of human transcripts might form sense-antisense pairs. , 2004, Nucleic acids research.