The GIS2 Gene Is Repressed by a Zinc-Regulated Bicistronic RNA in Saccharomyces cerevisiae.

Zinc homeostasis is essential for all organisms. The Zap1 transcriptional activator regulates these processes in the yeast . During zinc deficiency, Zap1 increases expression of zinc transporters and proteins involved in adapting to the stress of zinc deficiency. Transcriptional activation by Zap1 can also repress expression of some genes, e.g., . In zinc-replete cells, mRNA is produced with a short transcript leader that is efficiently translated. During deficiency, Zap1-dependent expression of an RNA with a longer transcript leader represses the promoter. This long leader transcript (LLT) is not translated due to the presence of small open reading frames upstream of the coding region. In this study, we show that the LLT RNA also plays a second function, i.e., repression of the adjacent gene. In generating the LLT transcript, RNA polymerase II transcribes through the promoter. Production of the LLT RNA correlates with the decreased expression of mRNA and mutations that prevent synthesis of the LLT RNA or terminate it before the promoter renders mRNA expression and Gis2 protein accumulation constitutive. Thus, we have discovered an unusual regulatory mechanism that uses a bicistronic RNA to control two genes simultaneously.