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Regulation and Function of the Dscam1 Extended 3’ UTR mRNA
AdvisorMiura, Pedro E.
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More than 50% of genes in species from Drosophila to human undergo alternative polyadenylation (APA). It has been shown that neuronal tissues are highly enriched for usage of transcripts with extended alternative 3’ untranslated regions, which are products of APA. Specific function of these longer 3’ UTR transcripts are largely unknown; however, because the 3’ UTR can regulate transcript stability, translational efficiency, and localization, it is plausible that 3’ UTR switching in nervous tissues may serve important biological functions. We chose to study the extended 3’ UTR of Dscam1 as it is one of several axon guidance genes that express an extended 3’ UTR mRNA isoform. We created a Dscam1 extended 3’ UTR mutant using the relatively new CRISPR/CAS9 system. We show that the Dscam1 extended 3’ UTR loss of function mutants have severe deficiencies in locomotor activity and display an increased mortality rate. We have identified that in S2 cells the RNA binding protein ELAV promotes use of the extended 3’ UTR of Dscam1 and also show that ELAV is capable of binding at least two putative binding sites located on the 3’ UTR of Dscam1. Elucidating the important function of these extended 3’ UTRs will benefit not only our knowledge of axon guidance, but may reveal the function of a pervasive neural phenomenon.