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

• Published in: Nucleic acids research Vol. 48; no. 15; pp. 8243 - 8254
• Main Author: Shuman, Stewart
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 04.09.2020
• Subjects: Gene Expression Regulation, Fungal; Homeostasis; Nutrients - metabolism; Phosphoglycerate Dehydrogenase - genetics; Phosphoglycerate Dehydrogenase - metabolism; Regulon; RNA, Long Noncoding - genetics; RNA, Messenger; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Saccharomycetales - genetics; Saccharomycetales - metabolism; Schizosaccharomyces - genetics; Schizosaccharomyces - metabolism; Schizosaccharomyces pombe Proteins - genetics; Schizosaccharomyces pombe Proteins - metabolism; Survey and Summary; Transcription, Genetic
• ISSN: 0305-1048; 1362-4962; 1362-4962
• DOI: 10.1093/nar/gkaa630

Abstract 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 SER3 is repressed under serine-replete conditions by transcription of an upstream SRG1 lncRNA that traverses the SER3 promoter and elicits occlusive nucleosome rearrangements. SER3 is de-repressed by serine withdrawal, which leads to shut-off of SRG1 synthesis. The fission yeast phosphate homeostasis (PHO) regulon comprises three phosphate acquisition genes – pho1, pho84, and tgp1 – that are repressed under phosphate-replete conditions by 5′ flanking lncRNAs prt, prt2, and nc-tgp1, respectively. lncRNA transcription across the PHO mRNA promoters displaces activating transcription factor Pho7. PHO mRNAs are transcribed during phosphate starvation when lncRNA synthesis abates. The PHO regulon is de-repressed in phosphate-replete cells by genetic manipulations that favor ‘precocious’ lncRNA 3′-processing/termination upstream of the mRNA promoters. PHO lncRNA termination is governed by the Pol2 CTD code and is subject to metabolite control by inositol pyrophosphates.