title: 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.
authors.affiliation: Wellcome Trust Centre for Cell Biology and Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, Max Born Crescent, Edinburgh EH9 3BF, Scotland, UK.
authors.forename: Ryan
authors.initials: R
authors.lastname: Ard
authors.affiliation: Wellcome Trust Centre for Cell Biology and Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, Max Born Crescent, Edinburgh EH9 3BF, Scotland, UK.
authors.forename: Pin
authors.initials: P
authors.lastname: Tong
authors.affiliation: Wellcome Trust Centre for Cell Biology and Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, Max Born Crescent, Edinburgh EH9 3BF, Scotland, UK.
authors.forename: Robin C
authors.initials: RC
authors.lastname: Allshire
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D025141:Drug Resistance, Fungal; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D012331:RNA, Fungal / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D012568:Schizosaccharomyces / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000935:Antifungal Agents; D026901:Membrane Transport Proteins; D012331:RNA, Fungal; D062085:RNA, Long Noncoding; C000602009:SPBC1271.09 protein, S pombe; C000602011:SPNCRNA.1343 long noncoding RNA, S pombe; D029702:Schizosaccharomyces pombe Proteins