Multifaceted mammalian transcriptome.

Despite surprisingly a small number of protein-coding gene in mammalian genomes, a large variety of different RNAs is being produced. These RNAs are amazingly different in their number, size, cell localization, and mechanism of actions. Although new classes of short RNAs (sRNAs) are being continuously discovered, it is not yet obvious how many of the sRNAs are originated. Altogether, the research in the recent few years has identified an unexpectedly rich variety of mechanisms by which noncoding RNAs act, suggesting that we have identified probably only few of the many potential functional mechanism and more investigation will be needed to comprehensively understand the complex nature and biology of mammalian RNAome. Here, we focus on various aspects of the diversity of the biological role of these nonprotein-coding RNAs (ncRNAs), with emphasis on functional mechanisms recently elucidated.

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

[2]  John N. Hutchinson,et al.  Widespread Monoallelic Expression on Human Autosomes , 2007, Science.

[3]  G. Tolstonog,et al.  Distinct roles for LINE-1 and HERV-K retroelements in cell proliferation, differentiation and tumor progression , 2007, Oncogene.

[4]  M. Krangel,et al.  Regulation of T cell receptor-alpha gene recombination by transcription. , 2006, Nature immunology.

[5]  Ana Serra Barros,et al.  Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript , 2007, Nature.

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

[7]  T. Kwok,et al.  Induction of drug resistance and transformation in human cancer cells by the noncoding RNA CUDR. , 2007, RNA.

[8]  M. Krangel,et al.  Noncoding transcription controls downstream promoters to regulate T‐cell receptor α recombination , 2007, The EMBO journal.

[9]  A. Evsikov,et al.  Retrotransposons regulate host genes in mouse oocytes and preimplantation embryos. , 2004, Developmental cell.

[10]  Gratien G. Prefontaine,et al.  Developmentally Regulated Activation of a SINE B2 Repeat as a Domain Boundary in Organogenesis , 2007, Science.

[11]  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.

[12]  William Stafford Noble,et al.  Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project , 2007, Nature.

[13]  Ravi Sachidanandam,et al.  Developmentally Regulated piRNA Clusters Implicate MILI in Transposon Control , 2007, Science.

[14]  R. Weiss,et al.  EGO, a novel, noncoding RNA gene, regulates eosinophil granule protein transcript expression. , 2007, Blood.

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

[16]  H. Chao,et al.  Natural Antisense mRNAs to Hyaluronan Synthase 2 Inhibit Hyaluronan Biosynthesis and Cell Proliferation* , 2005, Journal of Biological Chemistry.

[17]  D. Haussler,et al.  An RNA gene expressed during cortical development evolved rapidly in humans , 2006, Nature.

[18]  G. Hannon,et al.  The Piwi-piRNA Pathway Provides an Adaptive Defense in the Transposon Arms Race , 2007, Science.

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

[20]  D. Corey,et al.  Activating gene expression in mammalian cells with promoter-targeted duplex RNAs. , 2007, Nature chemical biology.

[21]  V. Kim MicroRNA biogenesis: coordinated cropping and dicing , 2005, Nature Reviews Molecular Cell Biology.

[22]  Piero Carninci,et al.  Tagging mammalian transcription complexity. , 2006, Trends in genetics : TIG.

[23]  M. Karin,et al.  A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas , 2007, Oncogene.

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

[25]  B. Cullen,et al.  The imprinted H19 noncoding RNA is a primary microRNA precursor. , 2007, RNA.

[26]  M. Oshimura,et al.  Suggestive evidence for chromosomal localization of non-coding RNA from imprinted LIT1 , 2007, Journal of Human Genetics.

[27]  P. Stadler,et al.  RNA Maps Reveal New RNA Classes and a Possible Function for Pervasive Transcription , 2007, Science.

[28]  Edwin Cuppen,et al.  Diversity of microRNAs in human and chimpanzee brain , 2006, Nature Genetics.

[29]  V. Orlando,et al.  Noncoding RNA synthesis and loss of Polycomb group repression accompanies the colinear activation of the human HOXA cluster. , 2006, RNA.

[30]  I. Grummt,et al.  Intergenic transcripts regulate the epigenetic state of rRNA genes. , 2006, Molecules and Cells.

[31]  D. Haussecker,et al.  Dicer-Dependent Turnover of Intergenic Transcripts from the Human β-Globin Gene Cluster , 2005, Molecular and Cellular Biology.

[32]  N. Proudfoot Transcriptional interference and termination between duplicated α-globin gene constructs suggests a novel mechanism for gene regulation , 1986, Nature.

[33]  V. Babich,et al.  Clusters of regulatory signals for RNA polymerase II transcription associated with Alu family repeats and CpG islands in human promoters. , 2004, Genomics.

[34]  P. D. de Jong,et al.  L1 retrotransposition can occur early in human embryonic development. , 2007, Human molecular genetics.

[35]  D. Corey,et al.  Inhibiting gene expression at transcription start sites in chromosomal DNA with antigene RNAs , 2005, Nature chemical biology.

[36]  A. Hochberg,et al.  The H19 Non-Coding RNA Is Essential for Human Tumor Growth , 2007, PloS one.

[37]  David Haussler,et al.  Thousands of human mobile element fragments undergo strong purifying selection near developmental genes , 2007, Proceedings of the National Academy of Sciences.

[38]  Atif Shahab,et al.  Fusion transcripts and transcribed retrotransposed loci discovered through comprehensive transcriptome analysis using Paired-End diTags (PETs). , 2007, Genome research.

[39]  C. Sander,et al.  A novel class of small RNAs bind to MILI protein in mouse testes , 2006, Nature.

[40]  C. Ponting,et al.  Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs. , 2007, Genome research.

[41]  K. Shearwin,et al.  Transcriptional interference--a crash course. , 2005, Trends in genetics : TIG.

[42]  Howard Y. Chang,et al.  Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs , 2007, Cell.

[43]  A. Feinberg,et al.  Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA , 2008, Nature.

[44]  Claes Wahlestedt,et al.  RNA interference is not involved in natural antisense mediated regulation of gene expression in mammals , 2006, Genome Biology.

[45]  F. Pauler,et al.  Silencing by imprinted noncoding RNAs: is transcription the answer? , 2007, Trends in genetics : TIG.

[46]  S. Antonarakis,et al.  Transcriptional activation by bidirectional RNA polymerase II elongation over a silent promoter , 2005, EMBO reports.

[47]  David I. Smith,et al.  Long, abundantly expressed non-coding transcripts are altered in cancer. , 2008, Human molecular genetics.

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

[49]  G. Finocchiaro,et al.  Localizing hotspots of antisense transcription , 2007, Nucleic acids research.

[50]  J. D. Engel,et al.  Transcriptional interference among the murine ß-like globin genes , 2007 .

[51]  C. Kanduri,et al.  The length of the transcript encoded from the Kcnq1ot1 antisense promoter determines the degree of silencing , 2006, The EMBO journal.

[52]  Brian S. Clark,et al.  The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator. , 2006, Genes & development.

[53]  Michael Thomas,et al.  MALAT-1, a novel noncoding RNA, and thymosin β4 predict metastasis and survival in early-stage non-small cell lung cancer , 2003, Oncogene.

[54]  N. Yang,et al.  L1 retrotransposition is suppressed by endogenously encoded small interfering RNAs in human cultured cells , 2006, Nature Structural &Molecular Biology.

[55]  J. D. Engel,et al.  Transcriptional interference among the murine beta-like globin genes. , 2007, Blood.

[56]  J. Takeda,et al.  Retrotransposons Influence the Mouse Transcriptome: Implication for the Divergence of Genetic Traits , 2007, Genetics.

[57]  J. Ortonne,et al.  Transposable B2 SINE elements can provide mobile RNA polymerase II promoters , 2001, Nature Genetics.

[58]  Ravi Sachidanandam,et al.  A germline-specific class of small RNAs binds mammalian Piwi proteins , 2006, Nature.

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

[60]  J. Goodrich,et al.  The SINE-encoded mouse B2 RNA represses mRNA transcription in response to heat shock , 2004, Nature Structural &Molecular Biology.