Berlin Institute for Medical Systems Biology (BIMSB) Max Delbrück Center (MDC) for Molecular Medi
Robert-Rössle-Straße 10 Building 89, Room 024 13125 Berlin, Germany
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Colaboration with Prof. Dr. Matthias Hentze
PROJECT INFORMATION :
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 58 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.
Focus of the group:
mRNP localization and local translation
KEY TECHNOLOGIES :
mESC neuronal differentiation system,
in vitro translation system
• Chekulaeva, M., Mathys, H., Zipprich, J., Attig, J., Colic, M., Parker, R., and Filipowicz, W. (2011). miRNA repression involves GW182-mediated recruitment of CCR4–NOT through conserved W-containing motifs. Nature Structural and Molecular Biology 18(11): 1218-26.
• Chekulaeva, M., Parker, R., and Filipowicz, W. (2010). The GW/WG repeats of Drosophila GW182 function as effector motifs for miRNA-mediated repression. Nucleic Acids Research 38(19): 6673-83.
• Chekulaeva, M., Filipowicz, W., and Parker, R. (2009). Multiple independent domains of dGW182 function in miRNA-mediated repression in Drosophila. RNA 15: 794-803.
• Chekulaeva, M. and Filipowicz, W. (2009). Mechanisms of miRNA-mediated post-transcriptional regulation in animal cells. Current Opinion in Cell Biology 21(3): 452-60.
• Chekulaeva, M., Hentze, M.W., and Ephrussi, A. (2006). Bruno acts as a dual repressor of oskar mRNA translation promoting mRNA oligomerization and formation of silencing particles. Cell 124: 521-533.