A high-resolution map of transcription in the yeast genome.

There is abundant transcription from eukaryotic genomes unaccounted for by protein coding genes. A high-resolution genome-wide survey of transcription in a well annotated genome will help relate transcriptional complexity to function. By quantifying RNA expression on both strands of the complete genome of Saccharomyces cerevisiae using a high-density oligonucleotide tiling array, this study identifies the boundary, structure, and level of coding and noncoding transcripts. A total of 85% of the genome is expressed in rich media. Apart from expected transcripts, we found operon-like transcripts, transcripts from neighboring genes not separated by intergenic regions, and genes with complex transcriptional architecture where different parts of the same gene are expressed at different levels. We mapped the positions of 3' and 5' UTRs of coding genes and identified hundreds of RNA transcripts distinct from annotated genes. These nonannotated transcripts, on average, have lower sequence conservation and lower rates of deletion phenotype than protein coding genes. Many other transcripts overlap known genes in antisense orientation, and for these pairs global correlations were discovered: UTR lengths correlated with gene function, localization, and requirements for regulation; antisense transcripts overlapped 3' UTRs more than 5' UTRs; UTRs with overlapping antisense tended to be longer; and the presence of antisense associated with gene function. These findings may suggest a regulatory role of antisense transcription in S. cerevisiae. Moreover, the data show that even this well studied genome has transcriptional complexity far beyond current annotation.

[1]  Franck Picard,et al.  A statistical approach for array CGH data analysis , 2005, BMC Bioinformatics.

[2]  R Parker,et al.  Analysis of the yeast genome: identification of new non-coding and small ORF-containing RNAs. , 1997, Nucleic acids research.

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

[4]  H. Park,et al.  Antisense-mediated inhibition of arginase (CAR1) gene expression in Saccharomyces cerevisiae. , 2001, Journal of Bioscience and Bioengineering.

[5]  Thomas Blumenthal,et al.  Caenorhabditis elegans operons: form and function , 2003, Nature Reviews Genetics.

[6]  P. Brown,et al.  Extensive Association of Functionally and Cytotopically Related mRNAs with Puf Family RNA-Binding Proteins in Yeast , 2004, PLoS biology.

[7]  Ronald W. Davis,et al.  Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. , 1999, Science.

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

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

[10]  C. Gissi,et al.  Untranslated regions of mRNAs , 2002, Genome Biology.

[11]  Rafael A. Irizarry,et al.  Bioinformatics and Computational Biology Solutions using R and Bioconductor , 2005 .

[12]  BMC Bioinformatics , 2005 .

[13]  A. Myers,et al.  Functional analysis of mRNA 3' end formation signals in the convergent and overlapping transcription units of the S. cerevisiae genes RHO1 and MRP2. , 1993, Nucleic acids research.

[14]  S. Kuersten,et al.  The power of the 3′ UTR: translational control and development , 2003, Nature Reviews Genetics.

[15]  Felix Naef,et al.  Solving the riddle of the bright mismatches: labeling and effective binding in oligonucleotide arrays. , 2002, Physical review. E, Statistical, nonlinear, and soft matter physics.

[16]  E. Lai Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation , 2002, Nature Genetics.

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

[18]  D J Lipman,et al.  Lineage-specific loss and divergence of functionally linked genes in eukaryotes. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Rafael A. Irizarry,et al.  Stochastic Models Inspired by Hybridization Theory for Short Oligonucleotide Arrays , 2005, J. Comput. Biol..

[20]  Madhur Kumar,et al.  Antisense RNA: Function and Fate of Duplex RNA in Cells of Higher Eukaryotes , 1998, Microbiology and Molecular Biology Reviews.

[21]  R. Russell,et al.  Animal MicroRNAs Confer Robustness to Gene Expression and Have a Significant Impact on 3′UTR Evolution , 2005, Cell.

[22]  Shuyun Dong,et al.  Genome-wide analysis of mRNAs regulated by the nonsense-mediated and 5' to 3' mRNA decay pathways in yeast. , 2003, Molecular cell.

[23]  C. Vaquero,et al.  Do natural antisense transcripts make sense in eukaryotes? , 1998, Gene.

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

[25]  Mark Gerstein,et al.  Issues in the analysis of oligonucleotide tiling microarrays for transcript mapping. , 2005, Trends in genetics : TIG.

[26]  B. Séraphin,et al.  Cryptic Pol II Transcripts Are Degraded by a Nuclear Quality Control Pathway Involving a New Poly(A) Polymerase , 2005, Cell.

[27]  김삼묘,et al.  “Bioinformatics” 특집을 내면서 , 2000 .

[28]  Felix Naef,et al.  Absolute mRNA concentrations from sequence-specific calibration of oligonucleotide arrays. , 2003, Nucleic acids research.

[29]  B. Barrell,et al.  Life with 6000 Genes , 1996, Science.

[30]  N. Gray,et al.  Regulation of mRNA translation by 5'- and 3'-UTR-binding factors. , 2003, Trends in biochemical sciences.

[31]  Martin Vingron,et al.  Variance stabilization applied to microarray data calibration and to the quantification of differential expression , 2002, ISMB.

[32]  C. Dieckmann,et al.  Regulation of poly(A) site choice of several yeast mRNAs. , 1998, Nucleic acids research.

[33]  D. Haussler,et al.  Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. , 2005, Genome research.

[34]  S. Eddy,et al.  Computational identification of non-coding RNAs in Saccharomyces cerevisiae by comparative genomics. , 2003, Nucleic acids research.

[35]  R. Simons,et al.  Antisense RNA control in bacteria, phages, and plasmids. , 1994, Annual review of microbiology.

[36]  Fred Winston,et al.  Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene , 2004, Nature.

[37]  Temple F. Smith,et al.  Probabilistic prediction of Saccharomyces cerevisiae mRNA 3'-processing sites. , 2002, Nucleic acids research.

[38]  B. Dujon,et al.  Large-scale exploration of growth inhibition caused by overexpression of genomic fragments in Saccharomyces cerevisiae , 2004, Genome Biology.

[39]  W. Xiao,et al.  Generation of an ilv bradytrophic phenocopy in yeast by antisense RNA , 1988, Current Genetics.

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

[41]  C R Cantor,et al.  Genomic detection of new yeast pre-mRNA 3'-end-processing signals. , 1999, Nucleic acids research.

[42]  A. Hinnebusch Translational regulation of GCN4 and the general amino acid control of yeast. , 2005, Annual review of microbiology.

[43]  Joseph M. Dale,et al.  Empirical Analysis of Transcriptional Activity in the Arabidopsis Genome , 2003, Science.

[44]  P. Brown,et al.  Genome-wide analysis of mRNA lengths in Saccharomyces cerevisiae , 2003, Genome Biology.

[45]  G. Storz,et al.  An abundance of RNA regulators. , 2005, Annual review of biochemistry.

[46]  B. Birren,et al.  Sequencing and comparison of yeast species to identify genes and regulatory elements , 2003, Nature.

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

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

[49]  Antoine Margeot,et al.  Genome‐wide analysis of mRNAs targeted to yeast mitochondria , 2002, EMBO reports.

[50]  C. Glover,et al.  Gene expression profiling for hematopoietic cell culture , 2006 .