Poster abstracts

Poster number 58 submitted by Andrew Weeks

Identification of a novel mechanism of zinc homeostasis using a fission yeast model system

Andrew T. Weeks (Department of Human Nutrition,The Ohio State University), Derek M. Boehm (Department of Molecular Genetics, The Ohio State University), Amanda J. Bird (Department of Human Nutrition, Department of Molecular Genetics, The Ohio State University)

Abstract:
Zinc is essential for all life. Within cells, zinc functions as a structural or catalytic cofactor for many enzymes including the highly conserved and abundant cytosolic Cu2+/ Zn2+ binding enzyme superoxide dismutase-1 (Sod1). Here we show that in the model system Schizosaccharomyces pombe, sod1 mRNA levels are decreased in zinc-limiting conditions. We also find that this regulation is not dependent upon Loz1, the major regulator of zinc homeostasis, and other stress-related transcription factors known to regulate sod1 gene expression, suggesting a novel regulatory mechanism. Using reporter analysis, we demonstrate that a 1.8 kb sod1 promoter is insufficient to confer regulation by zinc. On the other hand, a plasmid containing ~3 kb of sod1, inclusive of the 1.8 kb promoter through the sod1 3’ UTR is sufficient to confer zinc-dependent regulation. Further analyses revealed that Sod1 protein abundance is dependent upon zinc and that the sod1 ORF and 3’ UTR are sufficient for these zinc-dependent changes while the 3’ UTR alone or combined with the sod1 promoter are insufficient. Our roles reveal a novel regulatory mechanism that allow sod1 levels to be adjusted in response to zinc in a manner that is dependent upon both the sod1 ORF and 3’ UTR.

Keywords: sod1 , mRNA regulation, zinc-dependent