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FOR 655: Asymmetric protein sorting via localizd translation - The role of ZBP protein in directing mRNA localization and translation
Posttranscriptional control of gene expression by RNA-binding proteins (RBPs) and microRNAs (miRs) allows the spatiotemporal fine tuning of protein expression during development, differentiation but also in neoplastic cells. Spatial control of mRNA translation is frequently observed in developing neurons and requires the transport of translationally silenced mRNAs into neurites. It is assumed that this process is facilitated via cytoplasmic protein-RNA complexes, typically classified as mRNPs. Members of the RNA-binding IGF2BP (IGF2 mRNA binding protein) protein family, also termed ZBPs (Zipcode binding proteins), are essential regulators of spatially controlled protein synthesis in developing neurons. In the latter, fibroblasts but also tumor-derived cells, ZBP1 controls translation and in some cases transport of the ß-actin (ACTB) mRNA. Upon Src-mediated tyrosine phosphorylation of ZBP1, ACTB mRNA translation is activated. In neuronal growth cones this spatial control of ACTB protein synthesis is presumed to direct growth cone protrusion and guidance. With the projects proposed, we intend to characterize the composition and posttranslational modifications of ZBP1-containing mRNPs to decipher their role in directing ACTB mRNA translation in a spatiotemporal manner.
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