Coordinated remodeling of cellular metabolism during iron deficiency through targeted mRNA degradation
Abstract
Iron (Fe) is an essential micronutrient for virtually all organisms and serves as a co-factor for a wide variety of vital cellular processes. Although Fe deficiency is the primary nutritional disorder in the world, cellular responses to Fe deprivation are poorly understood. We have discovered a novel post-transcriptional regulatory process controlled by Fe deficiency, which coordinately drives widespread metabolic reprogramming. We demonstrate that in response to Fe deficiency the Saccharomyces cerevisiae Cth2 protein specifically down-regulates mRNAs encoding proteins that participate in many Fe-dependent processes. mRNA turnover requires the binding of Cth2, an RNA-binding protein conserved in plants and mammals, to specific AU-rich elements in the 3AE untranslated region of mRNAs targeted for degradation. These studies elucidate coordinated global metabolic reprogramming in response to Fe deficiency and identify a mechanism for achieving this by targeting specific mRNA molecules for degradation, thereby facilitating the utilization of limited cellular Fe levels.
Authors
Sergi Puig, Eric Askeland and Dennis J. Thiele
Contact
- Dennis J. Thiele (dennis.thiele@duke.edu)
