Gene loops enhance transcriptional directionality

Science. 2012 Nov 2;338(6107):671-5. doi: 10.1126/science.1224350. Epub 2012 Sep 27.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Exosome Multienzyme Ribonuclease Complex / metabolism
  • Genes, Fungal*
  • Genome, Fungal
  • Mutation
  • Nucleic Acid Conformation
  • Phosphoprotein Phosphatases / metabolism
  • Promoter Regions, Genetic
  • RNA Polymerase II / metabolism
  • RNA Stability
  • RNA, Fungal / genetics
  • RNA, Fungal / metabolism
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • RNA, Untranslated / genetics*
  • RNA, Untranslated / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription, Genetic*
  • mRNA Cleavage and Polyadenylation Factors / metabolism

Substances

  • RNA, Fungal
  • RNA, Messenger
  • RNA, Untranslated
  • SSU72 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • mRNA Cleavage and Polyadenylation Factors
  • RNA Polymerase II
  • Exosome Multienzyme Ribonuclease Complex
  • RRP6 protein, S cerevisiae
  • Phosphoprotein Phosphatases