Control of mRNA stability under stress conditions

• Applicant: Professor Dr. Georg Stoecklin
• Subject Area: Cell Biology
• Term: from 2009 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 140272780

A hallmark of living organisms is their ability to adapt to a changing environment by coping with physical stress such as UV irradiation, oxidative stress or heat shock. Individual cells adapt to these forms of stress by reducing their regular metabolism and investing available resources into the repair of stress-induced damage. We and others have found that stress inhibits the degradation of labile mRNAs. The molecular mechanism of stress-induced mRNA stabilization, however, is not known. We have shown that Caf1 is a major deadenylase in human cells, and our preliminary data indicate that deadenylation is the step primarily inhibited under stress conditions. Furthermore, we have identified the human ortholog of yeast Pat1, a protein important for the assembly of Processing (P)-bodies. Pbodies are cytoplasmic mRNA-protein aggregates involved in mRNA degradation and the suppression of translation. In this grant application we propose to analyze the mechanism by which mRNAs containing an AU-rich element or microRNA binding sites are stabilized by oxidative and anisomycininduced stress. Our specific aims are (1) to analyze the role of Caf1 in stress-induced inhibition of mRNA deadenylation, (2) to characterize the P-body assembly factor Pat1 and its target mRNAs, and (3) to investigate the composition of P-bodies under normal and stress conditions. The proposed work will allow us to identify basic regulatory mechanisms that control the stability of mRNAs containing AU-rich elements and microRNA binding sites.

• DFG Programme: Research Grants