Neuronal RNA-binding proteins in mRNA localization

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The double-stranded RNA-binding protein (dsRBP) Staufen2 (Stau2) critically contributes to the transport of mRNAs to dendrites of polarized neurons. Recently, we have identified the first set of physiological RNA targets of Stau2, including the regulator of small G protein signaling (Rgs4) mRNA, which is implicated in neuropsychiatric disorders. In this project, we wish to understand how Stau2 binds specifically to Rgs4 mRNA and what the implications for this transcript are. Stau2 together with the RBP Pumilio2 (Pum2) are part of RNA granules in mammalian neurons. Preliminary evidence indicates that both RBPs may functionally and physically interact with each other. Furthermore, Stau2 protein is significantly down-regulated in both Pum2-deficient neurons as well as in Pum2-deficient mice. The goal of this project is to study the mechanistic basis and functional implications of Stau2 binding to Rgs4 mRNA and the contribution of Pum2 to Stau2-mediated RNA binding. Our aim is to understand how Rgs4 mRNA is specifically recognized by Stau2 and what implications this has for Rgs4 transcript stability and localization.