Gene expression and protein synthesis remodeling in response to iron deficiency in yeast

Abstract

AbstractIron is an essential trace element that serves as a cofactor for enzymes involved in multiple metabolic pathways, including ribosome biogenesis, protein translation, DNA synthesis and repair, lipid metabolism, and mitochondrial oxidative phosphorylation. In eukaryotes, iron deficiency leads to coordinated changes in gene expression and protein translation that activate iron uptake and allow metabolic adaptations of iron-dependent processes. While transcriptional responses to iron deprivation have been extensively characterized, little is known about the role of iron in regulating protein synthesis. In this study, we performed a genome-wide analysis of protein translation in yeast to identify transcripts translationally regulated under iron deficiency. We show that, upon iron depletion, a large set of genes necessary for mitochondrial protein synthesis is specifically down-regulated at the translational level. We demonstrate that this regulation is mediated through the activity of Cth1 and Cth2 mRNA-binding proteins. In addition, we uncover that Fe deficiency affects protein translation by limiting the activity of the conserved ribosome recycling factor Rli1. Together, these studies identified genes and pathways that are translationally regulated in response to iron deficiency and revealed a role of iron in translational control.