Long non-coding RNA-mediated transcriptional interference of a permease gene confers drug tolerance in fission yeast

Abstract

Most long non-coding RNAs (lncRNAs) encoded by eukaryotic genomes remain uncharacterized. Here we focus on a set of intergenic lncRNAs in fission yeast. Deleting one of these lncRNAs exhibited a clear phenotype: drug sensitivity. Detailed analyses of the affected locus revealed that transcription of the nc-tgp1 lncRNA regulates drug tolerance by repressing the adjacent phosphate-responsive permease gene transporter for glycerophosphodiester 1 ( tgp1 ⁺ ). We demonstrate that the act of transcribing nc-tgp1 over the tgp1 ⁺ promoter increases nucleosome density, prevents transcription factor access and thus represses tgp1 ⁺ without the need for RNA interference or heterochromatin components. We therefore conclude that tgp1 ⁺ is regulated by transcriptional interference. Accordingly, decreased nc-tgp1 transcription permits tgp1 ⁺ expression upon phosphate starvation. Furthermore, nc-tgp1 loss induces tgp1 ⁺ even in repressive conditions. Notably, drug sensitivity results directly from tgp1 ⁺ expression in the absence of the nc-tgp1 RNA. Thus, transcription of an lncRNA governs drug tolerance in fission yeast.

Abstract

The presence of long non-coding RNAs (lncRNAs) is pervasive across genomes, yet few lncRNAs have clearly established mechanisms of action. Here the authors demonstrate that the fission yeast lncRNA nc-tgp1 regulates expression of the drug tolerance gene tgp1 ₊ via ⁺ transcriptional interference.