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Widespread bidirectional promoters are the major source of cryptic transcripts in yeast


Pervasive and hidden transcription is widespread in eukaryotes1,2,3,4, but its global level, the mechanisms from which it originates and its functional significance are unclear. Cryptic unstable transcripts (CUTs) were recently described as a principal class of RNA polymerase II transcripts in Saccharomyces cerevisiae5. These transcripts are targeted for degradation immediately after synthesis by the action of the Nrd1–exosome–TRAMP complexes6,7. Although CUT degradation mechanisms have been analysed in detail, the genome-wide distribution at the nucleotide resolution and the prevalence of CUTs are unknown. Here we report the first high-resolution genomic map of CUTs in yeast, revealing a class of potentially functional CUTs and the intrinsic bidirectional nature of eukaryotic promoters. An RNA fraction highly enriched in CUTs was analysed by a 3′ Long-SAGE (serial analysis of gene expression) approach adapted to deep sequencing. The resulting detailed genomic map of CUTs revealed that they derive from extremely widespread and very well defined transcription units and do not result from unspecific transcriptional noise. Moreover, the transcription of CUTs predominantly arises within nucleosome-free regions, most of which correspond to promoter regions of bona fide genes. Some of the CUTs start upstream from messenger RNAs and overlap their 5′ end. Our study of glycolysis genes, as well as recent results from the literature8,9,10,11, indicate that such concurrent transcription is potentially associated with regulatory mechanisms. Our data reveal numerous new CUTs with such a potential regulatory role. However, most of the identified CUTs corresponded to transcripts divergent from the promoter regions of genes, indicating that they represent by-products of divergent transcription occurring at many and possibly most promoters. Eukaryotic promoter regions are thus intrinsically bidirectional, a fundamental property that escaped previous analyses because in most cases divergent transcription generates short-lived unstable transcripts present at very low steady-state levels.

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Figure 1: Genome-wide analyses of 3′ SAGE-tag clusters.
Figure 2: Regulation of CUTs associated with TPI1 mRNAs.
Figure 3: Distribution of TA CUTs relative to NFRs.

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Raw data are available from ArrayExpress ( under accession number E-MTAB-75 for SAGE data and E-TABM-602 for tiling array data.


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We thank D. Libri for the gift of strains, D. Libri, C. Thermes, C. Saveanu and M. Fromont-Racine for discussions and for critical reading of the manuscript, staff of the Genoscope (Evry) for sequencing, and A. Doyen, L. Decourty, S. Clauder-Muenster and T. Bähr-Ivacevic for technical assistance. This work was supported by the Institut Pasteur, the CNRS, the ANR (CUT program), the European Science Foundation (RNA quality program), and the National Institutes of Health and the Deutsche Forschungsgemeinschaft. H.N. is supported by the ANR (CUT program).

Author Contributions H.N. performed the experimental work except the sequencing, which was performed at Genoscope, Evry, and the tiling array experiments, which were performed in the group of L.M.S. and analysed by Z.X.; C.M. performed most of the bioinformatics analyses with the help of Y.d’A.-C. for the NFRs analyses; A.J. and H.N. designed the research and A.J. supervised the work; and A.J., H.N. and C.M. wrote the manuscript.

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Correspondence to Alain Jacquier.

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This file contains Supplementary Figures S1-S10 with Legends, Supplementary Methods, Supplementary Data, Supplementary Tables 1-5 and Supplementary References (PDF 4680 kb)

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Neil, H., Malabat, C., d’Aubenton-Carafa, Y. et al. Widespread bidirectional promoters are the major source of cryptic transcripts in yeast. Nature 457, 1038–1042 (2009).

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