Research Article: Heavy metal sensitivities of gene deletion strains for ITT1 and RPS1A connect their activities to the expression of URE2, a key gene involved in metal detoxification in yeast

Date Published: September 19, 2018

Publisher: Public Library of Science

Author(s): Houman Moteshareie, Maryam Hajikarimlou, Alex Mulet Indrayanti, Daniel Burnside, Ana Paula Dias, Clara Lettl, Duale Ahmed, Katayoun Omidi, Tom Kazmirchuk, Nathalie Puchacz, Narges Zare, Sarah Takallou, Thet Naing, Raúl Bonne Hernández, William G. Willmore, Mohan Babu, Bruce McKay, Bahram Samanfar, Martin Holcik, Ashkan Golshani, Alvaro Galli.


Heavy metal and metalloid contaminations are among the most concerning types of pollutant in the environment. Consequently, it is important to investigate the molecular mechanisms of cellular responses and detoxification pathways for these compounds in living organisms. To date, a number of genes have been linked to the detoxification process. The expression of these genes can be controlled at both transcriptional and translational levels. In baker’s yeast, Saccharomyces cerevisiae, resistance to a wide range of toxic metals is regulated by glutathione S-transferases. Yeast URE2 encodes for a protein that has glutathione peroxidase activity and is homologous to mammalian glutathione S-transferases. The URE2 expression is critical to cell survival under heavy metal stress. Here, we report on the finding of two genes, ITT1, an inhibitor of translation termination, and RPS1A, a small ribosomal protein, that when deleted yeast cells exhibit similar metal sensitivity phenotypes to gene deletion strain for URE2. Neither of these genes were previously linked to metal toxicity. Our gene expression analysis illustrates that these two genes affect URE2 mRNA expression at the level of translation.

Partial Text

Heavy metals and metalloids comprise a group of elements that are loosely defined as relatively high-density transition metals and metalloids [1], [2]. Different metals are found in varied concentrations across the environment. Some of these heavy elements, such as iron (Fe), cobalt (Co) and zinc Zn, are essential nutrients, while others are relatively harmless at low concentrations such as rubidium (Ru), silver (Ag) and indium (In). At higher concentrations, all metals and metalloids derived from natural environment [3] or anthropogenic sources such as phosphate fertilizers, disinfectants, fungicides, sewage sludge, industrial waste, bad watering practices in agricultural lands, and dust from smelters [4], [5] are toxic to living cells [6], [7], [8]. Among these, arsenic (As) is one of the most toxic despite being the twentieth most abundant element on our planet. Its inorganic oxyanion forms including arsenite (As(III)) and arsenate (As(II)) are highly lethal to living organisms [9].




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