Gene loops enhance transcriptional directionality

TY - JOUR

T1 - Gene loops enhance transcriptional directionality

AU - Tan-Wong, Sue Mei

AU - Zaugg, Judith B

AU - Camblong, Jurgi

AU - Xu, Zhenyu

AU - Zhang, David W

AU - Mischo, Hannah E

AU - Ansari, Aseem Z

AU - Luscombe, Nicholas M

AU - Steinmetz, Lars M

AU - Proudfoot, Nick J

PY - 2012/11/2

Y1 - 2012/11/2

N2 - 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.

AB - 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.

KW - Exosome Multienzyme Ribonuclease Complex/metabolism

KW - Genes, Fungal

KW - Genome, Fungal

KW - Mutation

KW - Nucleic Acid Conformation

KW - Phosphoprotein Phosphatases/metabolism

KW - Promoter Regions, Genetic

KW - RNA Polymerase II/metabolism

KW - RNA Stability

KW - RNA, Fungal/genetics

KW - RNA, Messenger/genetics

KW - RNA, Untranslated/genetics

KW - Saccharomyces cerevisiae/genetics

KW - Saccharomyces cerevisiae Proteins/metabolism

KW - Transcription, Genetic

KW - mRNA Cleavage and Polyadenylation Factors/metabolism

U2 - 10.1126/science.1224350

DO - 10.1126/science.1224350

M3 - Article

C2 - 23019609

SN - 0036-8075

VL - 338

SP - 671

EP - 675

JO - Science

JF - Science

IS - 6107

ER -