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Yeast Cth2 protein represses the translation of ARE-containing mRNAs in response to iron deficiency

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Yeast Cth2 protein represses the translation of ARE-containing mRNAs in response to iron deficiency

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dc.contributor.author Ramos Alonso, Lucía
dc.contributor.author Romero Cuadrado, Antonia María
dc.contributor.author Soler, Maria Àngel
dc.contributor.author Perea García, Ana
dc.contributor.author Alepuz Martínez, Paula
dc.contributor.author Puig Todolí, Sergi
dc.contributor.author Martínez Pastor, María Teresa
dc.date.accessioned 2018-10-03T18:07:55Z
dc.date.available 2018-10-03T18:07:55Z
dc.date.issued 2018
dc.identifier.citation Ramos-Alonso, Lucía Romero Cuadrado, Antonia María Soler, Maria Àngel Perea García, Ana Alepuz Martínez, Paula Puig Todolí, Sergi Martínez Pastor, María Teresa 2018 Yeast Cth2 protein represses the translation of ARE-containing mRNAs in response to iron deficiency PLOS genetics 14 6 e1007476
dc.identifier.uri http://hdl.handle.net/10550/67701
dc.description.abstract In response to iron deficiency, the budding yeast Saccharomyces cerevisiae undergoes a metabolic remodeling in order to optimize iron utilization. The tandem zinc finger (TZF)-containing protein Cth2 plays a critical role in this adaptation by binding and promoting the degradation of multiple mRNAs that contain AU-rich elements (AREs). Here, we demonstrate that Cth2 also functions as a translational repressor of its target mRNAs. By complementary approaches, we demonstrate that Cth2 protein inhibits the translation of SDH4, which encodes a subunit of succinate dehydrogenase, and CTH2 mRNAs in response to iron depletion. Both the AREs within SDH4 and CTH2 transcripts, and the Cth2 TZF are essential for translational repression. We show that the role played by Cth2 as a negative translational regulator extends to other mRNA targets such as WTM1, CCP1 and HEM15. A structure-function analysis of Cth2 protein suggests that the Cth2 amino-terminal domain (NTD) is important for both mRNA turnover and translation inhibition, while its carboxy-terminal domain (CTD) only participates in the regulation of translation, but is dispensable for mRNA degradation. Finally, we demonstrate that the Cth2 CTD is physiologically relevant for adaptation to iron deficiency.
dc.language.iso eng
dc.relation.ispartof PLOS genetics, 2018, vol. 14, num. 6, p. e1007476
dc.subject RNA
dc.subject Expressió genètica
dc.title Yeast Cth2 protein represses the translation of ARE-containing mRNAs in response to iron deficiency
dc.type journal article es_ES
dc.date.updated 2018-10-03T18:07:55Z
dc.identifier.doi 10.1371/journal.pgen.1007476
dc.identifier.idgrec 127188
dc.rights.accessRights open access es_ES

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