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

Janet Taggart,Joshua J Coon,Colin W Macdiarmid,Erin Weisenhorn,Jason Russell,David J Eide,Yirong Wang

doi:10.3390/genes9090462

Janet Taggart, Joshua J Coon + Show 5 more

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https://doi.org/10.3390/genes9090462

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Abstract

Zinc homeostasis is essential for all organisms. The Zap1 transcriptional activator regulates these processes in the yeast Saccharomyces cerevisiae. 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., RTC4. In zinc-replete cells, RTC4 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 RTC4 promoter. This long leader transcript (LLT) is not translated due to the presence of small open reading frames upstream of the RTC4 coding region. In this study, we show that the RTC4 LLT RNA also plays a second function, i.e., repression of the adjacent GIS2 gene. In generating the LLT transcript, RNA polymerase II transcribes RTC4 through the GIS2 promoter. Production of the LLT RNA correlates with the decreased expression of GIS2 mRNA and mutations that prevent synthesis of the LLT RNA or terminate it before the GIS2 promoter renders GIS2 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.

Highlights

In prokaryotic organisms, there are many examples where the expression of multiple genes is controlled by a single regulatory region
While the observed changes in the level of many proteomics results with RNA-sequencing (RNA-seq) data from cells grown under the same zinc-replete proteins correlated with changes in their mRNA levels, several others did not
long leader transcript” (LLT) transcript, we found that it extends far beyond the RTC4 open reading frame (ORF) passing through transcript, we found that it extends far beyond the RTC4 ORF passing through the GIS2 promoter and ORF and into the divergently transcribed FOL1 gene [8]

Summary

Introduction

There are many examples where the expression of multiple genes is controlled by a single regulatory region. The classic bacterial operon comprises two or more protein-coding regions (i.e., cistrons) that are regulated by a single upstream promoter. Production of polycistronic mRNA allows for the co-regulated production of multiple, often functionally related proteins because prokaryotic ribosomes are capable of internal translation initiation. While it has been often suggested that mechanisms of multigene regulation exist in eukaryotes, specific examples are much less common. One mechanism of multigene regulation involves genes that are divergently transcribed and contain a common promoter region between them that controls both genes. Regulation of the GAL1 and GAL10 genes by Gal in Saccharomyces cerevisiae is one such example [1]

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