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: Ryan Ard, Pin Tong, Robin C Allshire
• Journal: Nature communications (Nat Commun) Vol. 5 Pg. 5576 (Nov 27 2014) ISSN: 2041-1723 [Electronic] England
• PMID: 25428589 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antifungal Agents
• Membrane Transport Proteins
• RNA, Fungal
• RNA, Long Noncoding
• SPBC1271.09 protein, S pombe
• SPNCRNA.1343 long noncoding RNA, S pombe
• Schizosaccharomyces pombe Proteins

Topics

• Antifungal Agents (pharmacology)
• Drug Resistance, Fungal
• Membrane Transport Proteins (genetics, metabolism)
• RNA Interference
• RNA, Fungal (genetics, metabolism)
• RNA, Long Noncoding (genetics, metabolism)
• Schizosaccharomyces (drug effects, enzymology, genetics)
• Schizosaccharomyces pombe Proteins (genetics, metabolism)
• Transcription, Genetic