Metabolic regulation of IMD2 transcription and an unusual DNA element that generates short transcripts

Mol Cell Biol. 2007 Apr;27(8):2821-9. doi: 10.1128/MCB.02159-06. Epub 2007 Feb 12.

Abstract

Transcriptional regulation of IMD2 in yeast (Saccharomyces cerevisiae) is governed by the concentration of intracellular guanine nucleotide pools. The mechanism by which pool size is measured and transduced to the transcriptional apparatus is unknown. Here we show that DNA sequences surrounding the IMD2 initiation site constitute a repressive element (RE) involved in guanine regulation that contains a novel transcription-blocking activity. When this regulatory region is placed downstream of a heterologous promoter, short poly(A)(+) transcripts are generated. The element is orientation dependent, and sequences within the normally transcribed and nontranscribed regions of the element are required for its activity. The promoter-proximal short RNAs are unstable and serve as substrates for the nuclear exosome. These findings support a model in which intergenic short transcripts emanating from upstream of the IMD2 promoter are terminated by a polyadenylation/terminator-like signal embedded within the IMD2 transcription start site.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Base Sequence
  • DNA, Fungal / genetics*
  • Exoribonucleases / genetics
  • Exosome Multienzyme Ribonuclease Complex
  • Gene Deletion
  • Guanine / pharmacology
  • IMP Dehydrogenase / genetics*
  • Molecular Sequence Data
  • Mutation / genetics
  • Poly A / genetics
  • Promoter Regions, Genetic / drug effects
  • Promoter Regions, Genetic / genetics
  • RNA Stability / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Regulatory Sequences, Nucleic Acid / drug effects
  • Regulatory Sequences, Nucleic Acid / genetics*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription, Genetic* / drug effects
  • mRNA Cleavage and Polyadenylation Factors / metabolism

Substances

  • DNA, Fungal
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • mRNA Cleavage and Polyadenylation Factors
  • RNA15 protein, S cerevisiae
  • Poly A
  • Guanine
  • IMD2 protein, S cerevisiae
  • IMP Dehydrogenase
  • Exoribonucleases
  • Exosome Multienzyme Ribonuclease Complex
  • RRP6 protein, S cerevisiae