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.

We thank Randy Shaw and Young Lee for plasmid and strain construction and early observations of RE function and J. Boss, C. Moran, and A. Corbett for helpful comments.

This work was supported by NIH grant GM46331.