Molecular mechanism of translation-independent mRNA targeting to the tubular and cortical endoplasmic reticulum network

• Antragsteller: Professor Dr. Ralf-Peter Jansen
• Fachliche Zuordnung: Zellbiologie
• Förderung: Förderung von 2009 bis 2013
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 164497376

In eukaryotes, directional movement of specific cytoplasmic mRNAs (mRNA localization) and their subsequent local translation is a powerful mechanism to achieve cellular asymmetry and is crucial for cell differentiation. Recently, co-localization of specific mRNAs and intracellular membranes in yeast and mammals has led to the hypothesis that their localized translation facilitates the translocation of encoded proteins into organelles. However, the underlying mechanism for this targeting is unknown. We have demonstrated that yeast localized ASH1 mRNA is co-transported with several other localized mRNAs and with tubular endoplasmic reticulum (ER) to the cell cortex. We now want to understand the biological function of mRNA – ER association for set of localized and non-localized mRNAs, using yeast as a model system. Association of ASH1 with ER membranes is translationindependent and requires the RNA-binding protein She2p, which binds purified ER membranes. We aim at defining the molecular basis of ER interaction with She2p and other RNA-binding proteins like Scp160p and Whi3p that might fulfill similar functions. Combining in vitro binding assays, live cell imaging, yeast genetics, and chemical crosslinking, we want to identify putative receptors in or at the ER membrane as well as analyze the role of proteins influencing ER shape and lipid composition in mRNA binding to the ER. Our studies should reveal the molecular mechanism of translation-independent mRNA association with intracellular membranes.

• DFG-Verfahren: Sachbeihilfen