Protein-RNA networks ALS
Start date: Aug 1, 2013,
End date: Jul 31, 2015
Interactions between proteins and RNAs regulate processing, localization, decay and translational regulation of mRNAs. Recently, it was revealed that the number of putative RBPs in mammalian cells is about three times larger than appreciated. However, the exposed interaction network was inspected only in a single given state; furthermore the functional gene expression mechanism is yet unknown. In my proposed project, we aim to inspect the differences in global protein-occupancy on mRNAs and identify the critical remodeling in protein-RNA interactions that drives the subcellular localization and translation of mRNAs. Our goal will be to understand the misregulated RNA networks in Amyotrophic-lateral-sclerosis (ALS), a common neuromuscular disorder. We will study mouse and human embryonic stem cells and induced pluripotent stem cells of ALS patients, and brain tissue of mouse ALS models. Protein-RNA interactions will be studied by crosslinking the cells in different biological states, purifying RNPs from different cellular fractions high-throughput sequencing on iCLIP produced libraries, and mRNA translation will be studied with ribosome profiling. The combinatorial statistical inference and state-of-the-art computational approaches will be used to interpret the relevant dynamic RNA networks. This work will aim to reveal how normal and dysfunctional dynamic RNA regulation controls translation in motor neurons.
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