Metabolic Regulation of IMD2 Transcription and an Unusual DNA Element That Generates Short Transcripts

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.

[1]  Sarah Ng,et al.  cis- and trans-Acting Determinants of Transcription Termination by Yeast RNA Polymerase II , 2006, Molecular and Cellular Biology.

[2]  M. Ares,et al.  Accumulation of unstable promoter-associated transcripts upon loss of the nuclear exosome subunit Rrp6p in Saccharomyces cerevisiae. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Fred Winston,et al.  in Saccharomyces cerevisiae , 2005 .

[4]  Brian D. Strahl,et al.  A Novel Domain in Set2 Mediates RNA Polymerase II Interaction and Couples Histone H3 K36 Methylation with Transcript Elongation , 2005, Molecular and Cellular Biology.

[5]  D. Reines,et al.  Detection of the mycophenolate-inhibited form of IMP dehydrogenase in vivo. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[6]  E. Cho,et al.  mRNA Capping Enzyme Activity Is Coupled to an Early Transcription Elongation , 2004, Molecular and Cellular Biology.

[7]  Fred Winston,et al.  Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene , 2004, Nature.

[8]  B. Daignan-Fornier,et al.  The Critical cis-Acting Element Required for IMD2 Feedback Regulation by GDP Is a TATA Box Located 202 Nucleotides Upstream of the Transcription Start Site , 2003, Molecular and Cellular Biology.

[9]  Judith W. Hyle,et al.  Functional Distinctions between IMP Dehydrogenase Genes in Providing Mycophenolate Resistance and Guanine Prototrophy to Yeast* , 2003, Journal of Biological Chemistry.

[10]  Nicholas D Bonawitz,et al.  Use of an in Vivo Reporter Assay to Test for Transcriptional and Translational Fidelity in Yeast* , 2002, The Journal of Biological Chemistry.

[11]  L. Prakash,et al.  Requirement of Yeast RAD2, a Homolog of Human XPG Gene, for Efficient RNA Polymerase II Transcription Implications for Cockayne Syndrome , 2002, Cell.

[12]  D. Tollervey,et al.  Processing of 3'-extended read-through transcripts by the exosome can generate functional mRNAs. , 2002, Molecular cell.

[13]  S. Squazzo,et al.  The Paf1 complex physically and functionally associates with transcription elongation factors in vivo , 2002, The EMBO journal.

[14]  Karen T. Smith,et al.  Regulation of an IMP Dehydrogenase Gene and Its Overexpression in Drug-sensitive Transcription Elongation Mutants of Yeast* , 2001, The Journal of Biological Chemistry.

[15]  T. Kodadek,et al.  The 19S regulatory particle of the proteasome is required for efficient transcription elongation by RNA polymerase II. , 2001, Molecular cell.

[16]  B. Daignan-Fornier,et al.  Transcriptional Regulation of the Yeast GMP Synthesis Pathway by Its End Products* , 2001, The Journal of Biological Chemistry.

[17]  Randal J. Shaw,et al.  Saccharomyces cerevisiae Transcription Elongation Mutants Are Defective in PUR5 Induction in Response to Nucleotide Depletion , 2000, Molecular and Cellular Biology.

[18]  L. Minvielle-Sebastia,et al.  mRNA polyadenylation and its coupling to other RNA processing reactions and to transcription. , 1999, Current opinion in cell biology.

[19]  L. Minvielle-Sebastia,et al.  Coupling termination of transcription to messenger RNA maturation in yeast. , 1998, Science.

[20]  J. Lis,et al.  Promoter-associated pausing in promoter architecture and postinitiation transcriptional regulation. , 1998, Cold Spring Harbor symposia on quantitative biology.

[21]  Michael Hampsey,et al.  A Review of Phenotypes in Saccharomyces cerevisiae , 1997, Yeast.

[22]  L. Minvielle-Sebastia,et al.  Mutations in the yeast RNA14 and RNA15 genes result in an abnormal mRNA decay rate; sequence analysis reveals an RNA-binding domain in the RNA15 protein , 1991, Molecular and cellular biology.