The Cth2 ARE-binding protein recruits the Dhh1 helicase to promote the decay of succinate dehydrogenase SDH4 mRNA in response to iron deficiency
The Cth2 ARE-binding protein recruits the Dhh1 helicase to promote the decay of succinate dehydrogenase SDH4 mRNA in response to iron deficiency
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DOI：
10.1074/jbc.m804910200
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发表时间：
2008-10-17
影响因子：
4.8
通讯作者：
Puig, Sergi
中科院分区：
文献类型：
--
作者：
Pedro-Segura, Elisa;Vergara, Sandra V.;Puig, Sergi
铁是一种必需的营养素，作为氧化还原辅因子参与广泛的细胞过程。为了应对铁缺乏，芽殖酵母酿酒酵母诱导Cth 1和Cth 2 mRNA结合蛋白的表达，以促进细胞代谢的全基因组重塑，从而有助于铁的最佳利用。Cth 1和Cth 2蛋白结合到许多编码铁依赖性途径中所涉及的蛋白质的mRNA的3 '-非翻译区内的特异性AU富集元件，从而促进其降解。在这里，我们表明，DEAD盒Dhh 1解旋酶在Cth 2介导的mRNA周转机制中起着至关重要的作用。酵母双杂交实验表明，Cth 2蛋白在体内与Dhh 1的羧基末端结构域相互作用。我们证明，琥珀酸脱氢酶SDH 4 mRNA的降解，一个已知的目标Cth 2在缺铁条件下，取决于Dhh 1。此外，我们将Cth 2蛋白定位于5'至3' mRNA衰变途径缺陷菌株的细胞质加工体。最后，捕获的SDH 4 mRNA中间体的Cth 2的降解支持5'到3'方向的mRNA周转。综上所述，这些结果表明，Cth 2蛋白招募Dhh 1解旋酶的ARE含有mRNA，以促进mRNA的衰变。
Iron is an essential nutrient that participates as a redox cofactor in a broad range of cellular processes. In response to iron deficiency, the budding yeast Saccharomyces cerevisiae induces the expression of the Cth1 and Cth2 mRNA-binding proteins to promote a genome-wide remodeling of cellular metabolism that contributes to the optimal utilization of iron. Cth1 and Cth2 proteins bind to specific AU-rich elements within the 3'-untranslated region of many mRNAs encoding proteins involved in iron-dependent pathways, thereby promoting their degradation. Here, we show that the DEAD box Dhh1 helicase plays a crucial role in the mechanism of Cth2-mediated mRNA turnover. Yeast two-hybrid experiments indicate that Cth2 protein interacts in vivo with the carboxyl-terminal domain of Dhh1. We demonstrate that the degradation of succinate dehydrogenase SDH4 mRNA, a known target of Cth2 on iron-deficient conditions, depends on Dhh1. In addition, we localize the Cth2 protein to cytoplasmic processing bodies in strains defective in the 5' to 3' mRNA decay pathway. Finally, the degradation of trapped SDH4 mRNA intermediates by Cth2 supports the 5' to 3' directionality of mRNA turnover. Taken together, these results suggest that Cth2 protein recruits the Dhh1 helicase to ARE-containing mRNAs to promote mRNA decay.