Translational Control in Neurons

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REVISED ABSTRACT: DESCRIPTION (provided by applicant): Long-term plastic changes at the synapse require de novo synthesis of proteins. Part of this requirement, it is suggested, is met by translation in situ of mRNAs that are localized to postsynaptic microdomains. Local translation, according to this model, provides the spatial and temporal specificity that is necessary for input-dependent modulations of synaptic protein repertoires. A central requisite for this concept is the control of gene expression at the level of translation. In particular, to afford spatio-temporal specificity, translational machinery in neurons will have to be tightly controlled such that protein synthesis is enabled only at the right place and at the right time. What are the functional mechanisms of such translational control, and how are they regulated? In the research project proposed here, it is hypothesized that small RNAs play an instrumental role in translational control mechanisms in neurons. Specifically, it is conjectured that non-translatable dendritic BC1 RNA operates as a repressor in the translation initiation pathway. To test this hypothesis, we will dissect structure-function relationships that are underlying BC1-mediated translational repression mechanisms. The analysis will be directed at the functional relevance of the BC1 domain architecture, and at the functional targets of BC1 RNA in the translation initiation pathway. BC1-mediated repression will also be functionally ascertained in living cells, using model systems such as Xenopus oocytes. It is the overall goal of the proposed research to elucidate mechanisms and functional significance of local translational control mediated by small neuronal RNAs.