Referencia

Sanvisens et al (2011) Molecular Cell 44(5): 759-769.

Autores

Nerea Sanvisens, Mari Carmen Bañó, Mingxia Huang y Sergi Puig

Resumen

Ribonucleotide reductase (RNR) is an essential enzyme required for DNA synthesis and repair. Although iron is necessary for class Ia RNR activity, little is known about the mechanisms that control RNR in response to iron deficiency. In this work, we demonstrate that yeast cells control RNR function during iron deficiency by redistributing the Rnr2-Rnr4 small subunit from the nucleus to the cytoplasm. Our data support a Mec1/Rad53-independent mechanism in which the iron-regulated Cth1/Cth2 mRNA-binding proteins specifically interact with the WTM1 mRNA in response to iron scarcity and promote its degradation. The resulting decrease in the nuclear-anchoring Wtm1 protein levels leads to the redistribution of the Rnr2-Rnr4 heterodimer to the cytoplasm, where it assembles as an active RNR complex and increases deoxyribonucleoside triphosphate levels. When iron is scarce, yeast selectively optimizes RNR function at the expense of other non-essential iron-dependent processes that are repressed, to allow DNA synthesis and repair.

Descripción

La ribonucleótido reductasa (RNR) es una enzima esencial dependiente de hierro que cataliza la reducción de ribonucleósidos difosfato en sus formas desoxi. Las RNRs eucariotas están formadas por una subunidad citoplásmica R1, en la que se encuentra el sitio catalítico, y una nuclear R2, que posee el centro de hierro. En este trabajo se describe que, en condiciones de deficiencia de hierro, la levadura S. cerevisiae prioriza la actividad RNR sobre otros procesos dependientes de hierro que no son esenciales para la célula. En estas condiciones, las proteínas Cth1 y Cth2 interaccionan con el mRNA WTM1 y promueven su degradación. La disminución de los niveles de proteína Wtm1, responsable del anclaje de la subunidad R2 al núcleo, permite la redistribución de ésta al citoplasma donde forma un complejo activo con la subunidad R1 permitiendo la síntesis de dNTPs.

Foto grupo febrero

REFERENCIA DEL GRUPO INVESTIGADOR
El grupo de Homeostasis de Hierro dirigido por el Dr. Sergi Puig se encuentra en el Instituto de Agroquímica y Tecnología de Alimentos del CSIC (www.iata.csic.es/spuig). Este grupo de investigación se inició en estrecha colaboración con la Dra. Lola Peñarrubia de la Universitat de València. En la actualidad, el grupo se centra en el estudio de los mecanismos de respuesta de la levadura Saccharomyces cerevisiae a la deficiencia de hierro con el objetivo de desarrollar aplicaciones en el área de la biotecnología de alimentos. Nerea Sanvisens es actualmente becaria predoctoral de la Universitat de València.

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