PhD Student, Medical Research Council- Laboratory of Molecular Biology (MRC-LMB)
Transportation of mRNAs in the nervous system
Subcellular mRNA localization plays an important role in regulating expression of different proteins in various compartments of cells. Local control over protein expression is particularly important in highly polarized cells such as neurons, which have different protein requirements in specialized regions such as dendrites and axons. Active transportation of mRNAs to their destinations requires trans-acting RNA localization signals or zipcodes, which are often present in the 3’UTR of the message. Zipcodes are detected by adaptors, which couple mRNA to molecular motors for active transportation. We have been investigating the mechanism of mRNA localization in Drosophila embryonic sensory axons by focusing on Ank2 mRNA, which we found in a screen for mRNAs localizing in the embryonic nervous system. We have shown that non-localizing overexpressed exogenous mRNAs do not localize into sensory axons and remain in the cell body, hence indicating an active process involved in Ank2 localization. We confirmed active localization of Ank2 by showing that it is dependent on kinesin and microtubule. To identify the putative localization element in the 3’UTR of the message, we used fully transgenic CRISPR approach to express gRNA and Cas9 endonuclease to reengineer the 3’UTR of Ank2 mRNA. Removing different region of Ank2 3’UTR resulted in defects in the nervous system although both Ank2 mRNA and protein are still present in neurons. One hypothesis to explain this phenotype is that absence of potentially important trans-acting factors bound to the Ank2 3’UTR results in the disruption of the embryonic nervous system, and we are currently investigating this hypothesis. We are introducing the powerful Drosophila embryonic nervous system as a new model for studying mRNA trafficking with a potential for studying general cargo trafficking in the future.