Bidirectional promoters generate pervasive transcription in yeast

By Zhenyu Xu, Wu Wei, J. Gagneur, F. Perocchi, Sandra Clauder-Münster, Jurgi Camblong, E. Guffanti, F. Stutz, Wolfgang Huber, Lars M. Steinmetz. Nature, 2009

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Genome-wide pervasive transcription has been reported in many eukaryotic organisms, revealing a highly interleaved transcriptome organization that involves hundreds of previously unknown non-coding RNAs. These recently identified transcripts either exist stably in cells (stable unannotated transcripts, SUTs) or are rapidly degraded by the RNA surveillance pathway (cryptic unstable transcripts, CUTs). One characteristic of pervasive transcription is the extensive overlap of SUTs and CUTs with previously annotated features, which prompts questions regarding how these transcripts are generated, and whether they exert function. Single-gene studies have shown that transcription of SUTs and CUTs can be functional, through mechanisms involving the generated RNAs or their generation itself. So far, a complete transcriptome architecture including SUTs and CUTs has not been described in any organism. Knowledge about the position and genome-wide arrangement of these transcripts will be instrumental in understanding their function. Here we provide a comprehensive analysis of these transcripts in the context of multiple conditions, a mutant of the exosome machinery and different strain backgrounds of Saccharomyces cerevisiae. We show that both SUTs and CUTs display distinct patterns of distribution at specific locations. Most of the newly identified transcripts initiate from nucleosome-free regions (NFRs) associated with the promoters of other transcripts (mostly protein-coding genes), or from NFRs at the 3′ ends of protein-coding genes. Likewise, about half of all coding transcripts initiate from NFRs associated with promoters of other transcripts. These data change our view of how a genome is transcribed, indicating that bidirectionality is an inherent feature of promoters. Such an arrangement of divergent and overlapping transcripts may provide a mechanism for local spreading of regulatory signals—that is, coupling the transcriptional regulation of neighbouring genes by means of transcriptional interference or histone modification.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/4f09cea6d368b573b3394304cfc799e7c29eac23

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Citations in the corpus

A Comparative Encyclopedia of DNA Elements in the Mouse Genome (2014, background): “We established 1:1 human-mouse orthologues for 151,257 internal exon pairs (Supplementary Table 16) and 204,887 intron pairs (Supplementary Table 17), and predicted 2,717 (3,446) novel human (respectively, mouse) exons (Supplementary Table 18).”
Long noncoding RNAs: functional surprises from the RNA world. (2009, background): “For example, small RNAs have been found to cluster near the 59 and 39 ends of genes (Han et al. 2007; Kapranov et al. 2007a; Core et al. 2008; He et al. 2008; Preker et al. 2008; Seila et al. 2008; Fejes-Toth et al. 2009; Neil et al. 2009; Taft et al. 2009; Xu et al. 2009).”
Genome-wide characterization of transcriptional start sites in humans by integrative transcriptome analysis. (2011, methodology): “Using this analysis, we expected to directly analyze the correlation between TSCs, pol II binding, and nucleosome structure for specialized cellular environments in humans (see Shivaswamy et al. 2008; Xu et al. 2009).”
The stress granule transcriptome reveals principles of mRNA accumulation in stress granules (2017, positive): “SUTs and CUTs were analyzed using the same method, but with a different annotation ﬁle gene annotation ﬁle that contained these transcript annotations (Xu et al., 2009).”
A quantitative atlas of polyadenylation in five mammals (2012, background): “Indeed, the functional roles of thousands of novel transcripts were widely debated, although it was later shown that a substantial class of ‘‘novel transcripts’’ plays more general roles in transcriptional regulation (Neil et al. 2009; Xu et al. 2009).”
Comprehensive comparative analysis of strand-specific RNA sequencing methods (2010, neutral): “To estimate this, we computed for each library the average coverage at each percentile of length from the annotated 5’ end to the annotated 3’ end of known transcripts 18 (Fig.”