yeast ζ‐crystallin/NADPH:quinone oxidoreductase (Zta1p) is under nutritional control by the target of rapamycin pathway and is involved in the regulation of argininosuccinate lyase mRNA half‐life

• Published in: The FEBS journal 2015-05, Vol.282 (10), p.1953-1964
• Main Authors: Crosas, Eva, Sumoy, Lauro, González, Eva, Díaz, Maykelis, Bartolomé, Salvador, Farrés, Jaume, Parés, Xavier, Biosca, Josep Antoni, Fernández, María Rosario
• Format: Article
• Language: English
• Subjects: amino acid starvation; amino acids; argininosuccinate lyase; Argininosuccinate Lyase - metabolism; AU‐rich binding protein; biosynthesis; crystallins; DNA; DNA - metabolism; Galactokinase - metabolism; gene expression regulation; genes; half life; humans; medium‐chain dehydrogenase/reductase; messenger RNA; NADP - metabolism; nucleotide sequences; nutrient availability; proteins; Quinone Reductases - genetics; Quinone Reductases - metabolism; Real-Time Polymerase Chain Reaction; RNA; RNA - metabolism; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; stress response; transcriptomics; Yeasts; zeta-Crystallins - genetics; zeta-Crystallins - metabolism
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.13246

The yeast ζ‐crystallin (Zta1p) is a quinone oxidoreductase belonging to the ζ‐crystallin family, with activity in the reduction of alkenal/alkenone compounds. Various biological functions have been ascribed to the members of this protein family, such as their ability to interact specifically with AU‐rich sequences in mRNA, and thus they have been proposed to act as AU‐rich element‐binding proteins (AREBPs). In this study, we evaluated the specificity of Zta1p for RNA versus DNA by means of a novel nonisotopic method for the in vitro quantitative detection of protein·RNA complexes. Through comparative transcriptomic analysis, we found that the lack of Zta1p negatively affects the expression of a group of genes involved in amino acid biosynthesis, the argininosuccinate lyase (ARG4) gene being one of them. Here, we propose that Zta1p participates in the post‐transcriptional regulation of ARG4 expression by increasing the ARG4 mRNA half‐life. In addition, expression of the ζ‐crystallin gene (ZTA1) is itself regulated by nutrient availability through the general amino acid control and target of rapamycin pathways. Our results shed new light on the ζ‐crystallin family members from yeast to humans as stress response proteins with a bifunctional role in the detoxification of alkenal and alkenone compounds, and the regulation of gene expression.