Article

A high-resolution map of transcription in the yeast genome

Department of Biochemistry, Stanford University, Palo Alto, California, United States
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 05/2006; 103(14):5320-5. DOI: 10.1073/pnas.0601091103
Source: PubMed

ABSTRACT 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.

Download full-text

Full-text

Available from: Lior David, Jul 04, 2015
0 Followers
 · 
181 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Diploid budding yeast undergoes rapid mitosis when it ferments glucose, and in the presence of a non-fermentable carbon source and the absence of a nitrogen source it triggers sporulation. Rich medium with acetate is a commonly used pre-sporulation medium, but our understanding of the molecular events underlying the acetate-driven transition from mitosis to meiosis is still incomplete. We identified 263 proteins for which mRNA and protein synthesis are linked or uncoupled in fermenting and respiring cells. Using motif predictions, interaction data and RNA profiling we find among them 28 likely targets for Ume6, a subunit of the conserved Rpd3/Sin3 histone deacetylase- complex regulating genes involved in metabolism, stress response and meiosis. Finally, we identify 14 genes for which both RNA and proteins are detected exclusively in respiring cells but not in fermenting cells in our sample set, including CSM4, SPR1, SPS4 and RIM4, which were thought to be meiosis-specific. Our work reveals intertwined transcriptional and post-transcriptional control mechanisms acting when a MATa/α strain responds to nutritional signals, and provides molecular clues how the carbon source primes yeast cells for entering meiosis.
    Journal of Proteomics 02/2015; 119. DOI:10.1016/j.jprot.2015.01.015 · 3.93 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The identification of important factors that affect nucleosome formation is critical to clarify nucleosome-forming mechanisms and the role of the nucleosome in gene regulation. Various features reported in the literature led to our hypothesis that multiple features can together contribute to nucleosome formation. Therefore, we compiled 779 features and developed a pattern discovery and scoring algorithm FFNs (Finding Features for Nucleosomes) to identify feature patterns that are differentially enriched in nucleosome-forming sequences and nucleosome-depletion sequences. Applying FFN to genome-wide nucleosome occupancy data in yeast and human, we identified statistically significant feature patterns that may influence nucleosome formation, many of which are common to the two species. We found that both sequence and structural features are important in nucleosome occupancy prediction. We discovered that, even for the same feature combinations, variations in feature values may lead to differences in predictive power. We demonstrated that the identified feature patterns could be used to assist nucleosomal sequence prediction.
    Genomics 08/2014; 104(2). DOI:10.1016/j.ygeno.2014.07.002 · 2.79 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: High-throughput gene expression analysis has revealed a plethora of previously undetected transcripts in eukaryotic cells. In this study, we investigate >1,100 unannotated transcripts in yeast predicted to lack protein-coding capacity. We show that a majority of these RNAs are enriched on polyribosomes akin to mRNAs. Ribosome profiling demonstrates that many bind translocating ribosomes within predicted open reading frames 10-96 codons in size. We validate expression of peptides encoded within a subset of these RNAs and provide evidence for conservation among yeast species. Consistent with their translation, many of these transcripts are targeted for degradation by the translation-dependent nonsense-mediated RNA decay (NMD) pathway. We identify lncRNAs that are also sensitive to NMD, indicating that translation of noncoding transcripts also occurs in mammals. These data demonstrate transcripts considered to lack coding potential are bona fide protein coding and expand the proteome of yeast and possibly other eukaryotes.