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.
| Iacoangeli, Anna; Adzovic, Linda; Chen, Emily Q et al. (2018) Regulatory BC200 RNA in peripheral blood of patients with invasive breast cancer. J Investig Med 66:1055-1063 |
| Iacoangeli, Anna; Dosunmu, Aderemi; Eom, Taesun et al. (2017) Regulatory BC1 RNA in cognitive control. Learn Mem 24:267-277 |
| Muslimov, Ilham A; Tuzhilin, Aliya; Tang, Thean Hock et al. (2014) Interactions of noncanonical motifs with hnRNP A2 promote activity-dependent RNA transport in neurons. J Cell Biol 205:493-510 |
| Eom, Taesun; Muslimov, Ilham A; Tsokas, Panayiotis et al. (2014) Neuronal BC RNAs cooperate with eIF4B to mediate activity-dependent translational control. J Cell Biol 207:237-52 |
| Iacoangeli, Anna; Tiedge, Henri (2013) Translational control at the synapse: role of RNA regulators. Trends Biochem Sci 38:47-55 |
| Muslimov, Ilham A; Patel, Mihir V; Rose, Arthur et al. (2011) Spatial code recognition in neuronal RNA targeting: role of RNA-hnRNP A2 interactions. J Cell Biol 194:441-57 |
| Eom, Taesun; Berardi, Valerio; Zhong, Jun et al. (2011) Dual nature of translational control by regulatory BC RNAs. Mol Cell Biol 31:4538-49 |
| Iacoangeli, Anna; Bianchi, Riccardo; Tiedge, Henri (2010) Regulatory RNAs in brain function and disorders. Brain Res 1338:36-47 |
| Zhong, Jun; Chuang, Shih-Chieh; Bianchi, Riccardo et al. (2010) Regulatory BC1 RNA and the fragile X mental retardation protein: convergent functionality in brain. PLoS One 5:e15509 |
| Zhong, Jun; Chuang, Shih-Chieh; Bianchi, Riccardo et al. (2009) BC1 regulation of metabotropic glutamate receptor-mediated neuronal excitability. J Neurosci 29:9977-86 |
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