Bioinformatics Analyses of the Transcriptome Reveal Ube3a-Dependent Effects on Mitochondrial-Related Pathways
UBE3A gene that encodes for the ubiquitin E3-ligase protein, UBE3A, is known to be implicated in several neurodevelopmental disorders. Lack of UBE3A expression results in Angelman syndrome a severe neurodevelopmental disorder, while its overexpression due to genomic duplication results in autism. The cellular roles of UBE3A are not fully understood, yet there is a growing body of evidence that these disorders involve mitochondrial dysfunction and increased oxidative stress. We aimed to utilize bioinformatics approaches in order to delineate the effects of Ube3a deletion on the expression of mitochondrial-related genes and pathways. For this, we generated an mRNA sequencing dataset from mouse embryonic fibroblasts (MEFs) that have a complete Ube3a gene deletion and wild-type controls. Since oxidative stress and mitochondrial dysregulation might not be exhibited in the resting baseline state, we also activated mitochondrial functioning in the cells of the two genotypes using TNFa or vehicle application. Transcriptomes of the four groups of MEFs, Ube3a+/+ and Ube3a-/-, with application of TNFa or vehicle, were analyzed using various bioinformatics tools and machine learning approaches. Our results indicate that Ube3a deletion differntially affects the genes expression profiles resulting in altering mitochondrial-associated pathways.