Translation regulation by RNA granules in mammalian neurons
We are studying localized protein synthesis in neurons that is shown to be important for long-term memory formation and synaptic plasticity (Dieck et al., 2014; Schuman et al., 2006; Holt et al., 2013). Ribosome the protein synthesis machine is an extensively studied macromolecular assembly that follows the genetic instructions to produce proteins in all organisms. Accumulating evidence reveals that protein synthesis levels of specific mRNAs are uniquely regulated in different cell types and will determine the cell-fate. Beside heterogeneity in the composition of the ribosome itself that provides the diversity in the ribosome activity, the cis-regulatory elements in the 5’ or 3’ untranslated (UTR) regions of mRNA do the same by orchestrating the timing, location and abundance of protein. In neurons, mRNAs localized in axons and dendrites are found in granules, together with ribosomes, collectively known as neuronal RNA granules that also contain specific RNA-binding proteins (RBP) required for transport and translational control. Only a subset of mRNAs that are involved in memory consolidation form RNA granules. For local targeting the mRNAs contain cis-acting elements that are found mainly in the 3’UTR. Neuronal RNA granules serve as the functional units for transport and translational control. The main interest is to shed a light on structural aspects of RBPs mediated mRNA inactivation in the neuronal RNA granules by using latest advances in the cryo-electron microscopy (cryo-EM) that allow to resolve the macromolecular structures at 3 angstrom resolution. Results would help to understand the memory formation in neuronal processes and RNA granule associated neurodegenerative disease.