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.
Highlights
Most long non-coding RNAs encoded by eukaryotic genomes remain uncharacterized
In S. pombe, long non-coding RNAs (lncRNAs) transcribed from centromeric outer repeats are processed by Dicer (Dcr1) into short interfering RNAs, which target the Clr[4] H3K9 methyltransferase via Ago[1] to establish repressive heterochromatin through the methylation of lysine 9 on histone H3
We identified two divergent transcriptional start sites arising within ncRNA.1343: one lncRNA transcribed towards the tgp[1] þ gene and the other in the opposite orientation. lacZ reporter assays demonstrate that the bidirectional promoter drives greater levels of transcription in the nc-tgp[1] direction (Supplementary Fig. 3)
Summary
Most long non-coding RNAs (lncRNAs) encoded by eukaryotic genomes remain uncharacterized. In a process termed ‘transcriptional interference’, serine-mediated repression of the budding yeast Saccharomyces cerevisiae SER3 gene is brought about by lncRNA transcription into the gene promoter, which increases nucleosome density and prevents transcription factor access[8,9,10]. These examples illustrate the positive and negative influence that lncRNA transcription can exert on gene regulation in response to environmental changes. The order of genes flanking the transcription units that encode lncRNAs can be preserved through evolution[30] (that is, synteny) and provides another criterion by which we can identify potential functionally conserved lncRNAs whose primary sequences might have diverged too much so as not to retain detectable homology
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
