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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

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.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.source	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.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	https://doi.org/10.1371/journal.pgen.1007476
dc.identifier.idgrec	127188
dc.rights.accessRights	open access	es_ES