title: Gene loops enhance transcriptional directionality.
abstract: Eukaryotic genomes are extensively transcribed, forming both messenger RNAs (mRNAs) and noncoding RNAs (ncRNAs). ncRNAs made by RNA polymerase II often initiate from bidirectional promoters (nucleosome-depleted chromatin) that synthesize mRNA and ncRNA in opposite directions. We demonstrate that, by adopting a gene-loop conformation, actively transcribed mRNA encoding genes restrict divergent transcription of ncRNAs. Because gene-loop formation depends on a protein factor (Ssu72) that coassociates with both the promoter and the terminator, the inactivation of Ssu72 leads to increased synthesis of promoter-associated divergent ncRNAs, referred to as Ssu72-restricted transcripts (SRTs). Similarly, inactivation of individual gene loops by gene mutation enhances SRT synthesis. We demonstrate that gene-loop conformation enforces transcriptional directionality on otherwise bidirectional promoters.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: Sue Mei
authors.initials: SM
authors.lastname: Tan-Wong
authors.forename: Judith B
authors.initials: JB
authors.lastname: Zaugg
authors.forename: Jurgi
authors.initials: J
authors.lastname: Camblong
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Xu
authors.forename: David W
authors.initials: DW
authors.lastname: Zhang
authors.forename: Hannah E
authors.initials: HE
authors.lastname: Mischo
authors.forename: Aseem Z
authors.initials: AZ
authors.lastname: Ansari
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Luscombe
authors.forename: Lars M
authors.initials: LM
authors.lastname: Steinmetz
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Proudfoot
mesh_terms: D063326:Exosome Multienzyme Ribonuclease Complex / Q000378:metabolism; D005800:Genes, Fungal; D016681:Genome, Fungal; D009154:Mutation; D009690:Nucleic Acid Conformation; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism; D020871:RNA Stability; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D039221:mRNA Cleavage and Polyadenylation Factors / Q000378:metabolism
chemical_list: D012331:RNA, Fungal; D012333:RNA, Messenger; D022661:RNA, Untranslated; C416934:SSU72 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D039221:mRNA Cleavage and Polyadenylation Factors; D012319:RNA Polymerase II; D063326:Exosome Multienzyme Ribonuclease Complex; C112610:RRP6 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases