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Negative Feedback Regulation of the Yeast Cth1 and Cth2 mRNA Binding Proteins Is Required for Adaptation to Iron Deficiency and Iron Supplementation

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Negative Feedback Regulation of the Yeast Cth1 and Cth2 mRNA Binding Proteins Is Required for Adaptation to Iron Deficiency and Iron Supplementation

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dc.contributor.author Martínez-Pastor, Mar es_ES
dc.contributor.author Vergara, Sandra V. es_ES
dc.contributor.author Puig Todolí, Sergi es_ES
dc.contributor.author Thiele, Dennis J. es_ES
dc.date.accessioned 2015-06-18T12:29:20Z
dc.date.available 2015-06-18T12:29:20Z
dc.date.issued 2013 es_ES
dc.identifier.citation Molecular and Cellular Biology Vol. 33 Issue 11: pp. 2178-2187 es_ES
dc.identifier.uri http://hdl.handle.net/10550/44469
dc.description.abstract Iron (Fe) is an essential element for all eukaryotic organisms because it functions as a cofactor in a wide range of biochemical processes. Cells have developed sophisticated mechanisms to tightly control Fe utilization in response to alterations in cellular demands and bioavailability. In response to Fe deficiency, the yeast Saccharomyces cerevisiae activates transcription of the CTH1 and CTH2 genes, which encode proteins that bind to AU-rich elements (AREs) within the 3′ untranslated regions (3′UTRs) of many mRNAs, leading to metabolic reprogramming of Fe-dependent pathways and decreased Fe storage. The precise mechanisms underlying Cth1 and Cth2 function and regulation are incompletely understood. We report here that the Cth1 and Cth2 proteins specifically bind in vivo to AREs located at the 3′UTRs of their own transcripts in an auto- and cross-regulated mechanism that limits their expression. By mutagenesis of the AREs within the CTH2 transcript, we demonstrate that a Cth2 negative-feedback loop is required for the efficient decline in Cth2 protein levels observed upon a rapid rise in Fe availability. Importantly, Cth2 autoregulation is critical for the appropriate recovery of Fe-dependent processes and resumption of growth in response to a change from Fe deficiency to Fe supplementation. es_ES
dc.title Negative Feedback Regulation of the Yeast Cth1 and Cth2 mRNA Binding Proteins Is Required for Adaptation to Iron Deficiency and Iron Supplementation es_ES
dc.type journal article es_ES
dc.identifier.doi 10.1128/MCB.01458-12 es_ES
dc.identifier.idgrec 090337 es_ES

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