Deciphering the molecular mechanisms of autism: A computational search for differential poly-adenylation events in neurexin-deficient worms (360G-Wellcome-211565_Z_18_Z)

Autism Spectrum Disorder (ASD) is the most prevalent neurodevelopmental disorder, but, despite a large body of studies, its molecular basis remains largely unknown. Meta-analysis of public transcriptomic data has suggested that the mechanism of alternative poly-adenylation (APA) might be dysregulated in the autistic brain. APA determines the length of the transcripts’ tails and thus indirectly controls temporal and spatial regulation of gene expression in mammalian cells by including or excluding regulatory elements from the 3’ untranslated region. APA has been implicated in disease, most notably cancer, but its link to ASD was only recently suggested and warrants further investigation. To circumvent challenges associated with using human tissue, this project suggests testing the presence of differential poly-adenylation events in a very simple model of autism, the neurexin-deficient C. elegans. Nematode worms lacking neurexin have been suggested as simple models for the study of molecular perturbations in ASD. This project will employ bioinformatics approaches to search in-house RNA-seq data of eight samples from wild-type and neurexin-deficient worms for significantly different APA events. Results from this study could be compared to findings in the autistic brain data and could help us design experiments to better understand the origin and effects of this dysregulation.