Deciphering the roles of neurite-targeted RBPs in mRNA localization and local translation

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RNA localization and local translation are important biological processes that underlie establishment of body axis, cell migration and synaptic plasticity. They are mediated by RNA binding proteins (RBPs) binding to specific cis-regulatory elements in mRNAs and mediating their localization, translation and stability. However, so far there have been few comprehensive studies of localized RBPs and their target mRNAs in mammalian cells. Using neurite/soma fractionation scheme, we have conducted a genome-wide screen for local proteome and transcriptome of neurons differentiated from mouse embryonic stem cells. This application is within the frame of SPP 1935 (Deciphering the mRNP code: RNA-bound Determinants of Post-transcriptional Gene Regulation), therefore here we are focusing on neurite-enriched RBPs (mRNA-interactome group) identified in our screen. We propose to dissect the roles of these RBPs in localization, local translation and stability of their targets, using CLIP and RIP assays, combined with spatial proteomic, transcriptomic and ribosome profiling analyses of neurite and soma compartments. The proposed research has the potential to substantially advance our understanding of mRNP function in spatial dimension.