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Description
The regulation of protein expression by cytoplasmic polyadenylation in neurons was demonstrated for a few
transcripts but was challenging to study due to the absence of reliable, quantitative methods. With the new
emerging technology of direct RNA sequencing on nanopores, it is now possible to sequence entire mRNA
molecules including the poly(A) tails. In the proposed project we will employ this method to characterize the
genome-wide mRNA poly(A) tail dynamics during neural activity-dependent synaptic plasticity. This initial
discovery stage will be followed by analyses of synaptic activity-dependent protein synthesis and plasticity.
After identifying the fraction of synaptic mRNAs that undergo cytoplasmic polyadenylation, we will search for
enzymes responsible for this process using in-house generated unique KO and knock-in mouse models.
Finally, we aim to elucidate mechanisms by which specific mRNAs are selected for cytoplasmic
polyadenylation.
In sum, this project, thanks to a combination of contemporary transcriptomic approaches with functional
studies on mouse KO models, will provide the first comprehensive picture of the role of cytoplasmic
polyadenylation in the regulation of local protein synthesis at synapses. The expertise of three partners from
Poland and Norway is indispensable for the success of this project.