XUT
XUT, a novel class of antisense regulatory ncRNA in yeast
Non-coding (nc)RNAs are key players in numerous biological processes such as gene regulation, chromatin domain formation and genome stability. However, despite recent evidence showing that pervasive transcription is broader than previously thought, only a few antisense long regulatory ncRNAs acting in transcriptional gene silencing in eukaryotes have been described. In S. cerevisiae, the characterized cryptic regulatory ncRNA are controlled by the Xrn1 5'-3' RNA exonuclease, but their generalization remains elusive. Here, using strand-specific RNA-seq, we identify a novel class of 1,658 Xrn1-sensitive Unstable Transcripts (XUTs) in which 66% are antisense to open reading frames (ORF). These transcripts are polyadenylated and RNA Polymerase II (RNAPII)-dependent. The majority of XUTs strongly accumulate in lithium-containing media, suggesting that they might play a role in adaptive responses to physiological stress. Strikingly, RNAPII ChIP-seq analysis of Xrn1-deficient strains revealed a significant decrease of RNAPII occupancy over 297 genes with antisense XUT. Those genes show an unusual bias for H3K4me3 mark and require the Set1 histone H3 lysine 4 methyl-transferase for silencing. Furthermore, abolishing H3K4me3 triggers the silencing of other genes with antisense XUT, suggesting that H3K4me3 antagonizes H3K4me2/1 repressive activity. Our results demonstrate that antisense ncRNA-mediated regulation is a general regulatory pathway for gene expression in S. cerevisiae. They support a model where antisense ncRNA-dependent gene regulation is also broadly mediated by trans-acting ncRNA and histone marks.