Theme 4 <i>In Vivo</i> Experimental Models

Background: Most human genes have multiple polyadenylation sites and the choice of site (alternative polyadenylation; APA) varies developmentally and spatially.ALS-associated TDP-43 proteinopathy has recently been shown to impact APA in human cell lines and patient tissues (1-3).It has not yet been shown whether these changes are recapitulated in Drosophila models of ALS, which could open new avenues of investigation and therapeutics.Objectives: In this study, we computationally investigated disease-associated APA in Drosophila and compared it to human data to determine the extent of flies modeling of this facet of ALS.Methods: RNA-seq data from previous studies of Drosophila models of ALS (4,5) were mined for APA analysis using two programs, TAPAS and QAPA.These studies included Tagged Ribosome Affinity Purifications (TRAP) and RNA immunoprecipitation (RIP) experiments which were used to filter APA genes for ribosome and TDP-43 complex associations.Results: There were 780 genes that exhibited APA in models of TDP-43 proteinopathy based on overexpression of wild-type or mutant TDP-43.Of these, 43 showed differential association with the ribosome.Several of these genes are already linked to