The Response of Schizosaccharomyces pombe to Zinc Deficiency

Institute of Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, NE2 4HH UK; The Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1HH UK

^* To whom correspondence should be addressed. Email: S.K.Whitehall{at}ncl.ac.uk.

	Abstract

A component of the cellular response to zinc deficiency operates via control of transcript abundance. Therefore, microarray analysis was employed to identify Schizosaccharomyces pombe genes whose mRNA levels are regulated by intracellular zinc status. A set of 57 genes was identified whose mRNA levels were substantially reduced in response to zinc deficiency, while the mRNA levels of 63 genes were increased by this condition. In order to investigate the mechanisms that control these responses, a genetic screen was employed to identify mutants with defective zinc-responsive gene expression. Two strains (II-1 and V7) that were identified by this screen harbour mutations that are linked to zrt1⁺, which encodes a putative ZIP zinc-uptake transporter. Importantly, zrt1⁺ mRNA levels are increased in response to zinc deprivation and cells lacking functional Zrt1 are highly impaired in their ability to proliferate at limiting zinc concentrations. Furthermore, zrt1 null cells were found to have severely reduced zinc contents, indicating that Zrt1 functions as a key regulator of intracellular zinc levels in fission yeast. Deletion of fet4⁺, another zinc-responsive gene encoding a putative metal ion transporter, exacerbated the phenotypes associated with loss of Zrt1 suggesting that Fet4 also plays a role in zinc uptake under limiting conditions.