The Cth2 ARE-binding protein recruits the Dhh1 helicase to promote the decay of succinate dehydrogenase SDH4 mRNA in response to iron deficiency.
Iron is an essential nutrient that participates as a redox co-factor 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.
Pedro-Segura
Elisa
E
Departament de Bioquímica i Biologia Molecular, Universitat de València, Avenida Doctor Moliner 50, E-46100, Burjassot, València, Spain.
Vergara
Sandra V
SV
Rodríguez-Navarro
Susana
S
Parker
Roy
R
Thiele
Dennis J
DJ
Puig
Sergi
S
D003593:Cytoplasm / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D005690:Galactose / Q000737:chemistry; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013385:Succinate Dehydrogenase / Q000378:metabolism*; D051816:Tristetraprolin / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C091790:TIS11 protein, S cerevisiae; D051816:Tristetraprolin; D007501:Iron; D013385:Succinate Dehydrogenase; C445083:DHH1 protein, S cerevisiae; D053487:DEAD-box RNA Helicases; D005947:Glucose; D005690:Galactose