Transcriptional interference at tandem lncRNA and protein-coding genes: an emerging theme in regulation of cellular nutrient homeostasis

摘要

Tandem transcription interference occurs when the act of transcription from an upstream promoter suppresses utilization of a co-oriented downstream promoter. Because eukaryal genomes are liberally interspersed with transcription units specifying long non-coding (lnc) RNAs, there are many opportunities for lncRNA synthesis to negatively affect a neighboring protein-coding gene. Here, I review two eukaryal systems in which lncRNA interference with mRNA expression underlies a regulated biological response to nutrient availability. Budding yeast is repressed under serine-replete conditions by transcription of an upstream lncRNA that traverses the promoter and elicits occlusive nucleosome rearrangements. is de-repressed by serine withdrawal, which leads to shut-off of synthesis. The fission yeast phosphate homeostasis ( ) regulon comprises three phosphate acquisition genes – , , and – that are repressed under phosphate-replete conditions by 5′ flanking lncRNAs , , and , respectively. lncRNA transcription across the mRNA promoters displaces activating transcription factor Pho7. mRNAs are transcribed during phosphate starvation when lncRNA synthesis abates. The regulon is de-repressed in phosphate-replete cells by genetic manipulations that favor ‘precocious’ lncRNA 3′-processing/termination upstream of the mRNA promoters. lncRNA termination is governed by the Pol2 CTD code and is subject to metabolite control by inositol pyrophosphates.