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XUTs are a class of Xrn1-sensitive antisense regulatory non-coding RNA in yeast


Non-coding (nc)RNAs are key players in numerous biological processes such as gene regulation, chromatin domain formation and genome stability1,2. Large ncRNAs interact with histone modifiers3,4,5 and are involved in cancer development6, X-chromosome inactivation7 and autosomal gene imprinting8. However, despite recent evidence showing that pervasive transcription is more widespread than previously thought9, only a few examples mediating gene regulation in eukaryotes have been described10. In Saccharomyces cerevisiae, the bona-fide regulatory ncRNAs are destabilized by the Xrn1 5′–3′ RNA exonuclease11,12 (also known as Kem1), but the genome-wide characterization of the entire regulatory ncRNA family remains elusive. Here, using strand-specific RNA sequencing (RNA-seq), we identify a novel class of 1,658 Xrn1-sensitive unstable transcripts (XUTs) in which 66% are antisense to open reading frames. These transcripts are polyadenylated and RNA polymerase II (RNAPII)-dependent. The majority of XUTs strongly accumulate in lithium-containing media, indicating that they might have a role in adaptive responses to changes in growth conditions. Notably, RNAPII chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) analysis of Xrn1-deficient strains revealed a significant decrease of RNAPII occupancy over 273 genes with antisense XUTs. These genes show an unusual bias for H3K4me3 marks and require the Set1 histone H3 lysine 4 methyl-transferase for silencing. Furthermore, abolishing H3K4me3 triggers the silencing of other genes with antisense XUTs, supporting a model in which H3K4me3 antagonizes antisense ncRNA repressive activity. Our results demonstrate that antisense ncRNA-mediated regulation is a general regulatory pathway for gene expression in S. cerevisiae.

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Figure 1: Cytoplasmic 5′–3′ RNA decay controls a class of cryptic ncRNA.
Figure 2: XUT ncRNAs accumulate in wild-type cells grown in presence of lithium.
Figure 3: Transcriptional gene silencing correlates with antisense XUT accumulation.
Figure 4: Antisense XUTs mediate transcriptional gene silencing through Set1-dependent histone methylation.

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Sequence Read Archive

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Sequence data are publicly available at NCBI Sequence Read Archive under accession number SRA030505 and at


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We thank B. Séraphin, L. Bénard and J. O’Sullivan for support and advice; B. Dichtl for insights into lithium treatment data normalization; M. Wéry and A. Taddei for helpful discussions; A. Johnson, T. Kouzarides and V. Géli for generous gift of plasmids and strains. Special thanks to M. Descrimes, C. Jubin and S. Lair for technical assistance. We thank L. Steinmetz and M. Chodder for sharing unpublished results. E.L.V.D. benefits from an FRM fellowship. This work has benefited from facilities and expertise of the IMAGIF sequencing platform (Centre de Recherche de Gif). This work was financially supported by the Canceropole Ile de France, the ANR “REGULncRNA” and ERC “EPIncRNA” starting grant.

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Authors and Affiliations



E.L.V.D. performed molecular biology experiments, RNA-seq, ChIP-seq libraries and sequencing on the ILLUMINA platform. C.L.C., Y.D.-C., M.S. and C.T. performed statistical and bioinformatic analyses. S.G., M.K., V.R. and C.B. provided technical assistance to molecular biology experiments. A.M., C.T., E.L.V.D. and C.L.C. designed the experiments. P.L.-N. and S.L. performed RNA-seq libraries and NGS sequencing on the SOLiD platform; A.N. managed sequencing on the SOLiD platform. E.L.V.D., C.L.C. and A.N. contributed to the writing. C.T. and A.M. wrote the paper. C.T. and A.M. planned the project.

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Correspondence to C. Thermes or A. Morillon.

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The authors declare no competing financial interests.

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van Dijk, E., Chen, C., d’Aubenton-Carafa, Y. et al. XUTs are a class of Xrn1-sensitive antisense regulatory non-coding RNA in yeast. Nature 475, 114–117 (2011).

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