Intergenic non-coding transcription utilises an RNA-based mechanism to drive transcriptional interference. Schizosaccharomyces pombe

Recent studies have revealed that eukaryotic genomes are pervasively transcribed by RNA polymerase II, producing a plethora of non-coding RNAs which frequently overlap protein-coding genes. Despite the fact that overlapping transcription is well known to repress transcription initiation from downstream promoters, the mechanism behind this phenomenon has remained elusive. It was proposed that transcriptional interference relies on the act of transcription rather than the RNA itself to block access of the transcription machinery to downstream promoters. Here, we demonstrate that an RNA and chromatin-dependent mechanism is responsible for transcriptional interference in fission yeast. This relies on co-transcriptional recruitment of the histone deacetylase Clr3 to nascent non-coding RNA, leading to formation of hypoacetylated chromatin and repression of the downstream protein-coding gene. Our findings highlight the unexpected requirement for RNA as well as trans-acting protein factors in mediating the repressive effects imposed on gene expression through overlapping non-coding transcription. Overall design: Two replicates of Clr3-TAP were analysed for PAR-CLIP together with a no cross-link control. Three replicates of each wild-type and seb1-1 were analysed for RNA-seq.