Bioinformatics Analyses of the Transcriptome Reveal Ube3a-Dependent Effects on Mitochondrial-Related Pathways
| Autor: | Lilach Simchi, Hanoch Kaphzan, Julia Panov, Yonatan Feuermann |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
congenital hereditary and neonatal diseases and abnormalities Ubiquitin-Protein Ligases Induced Pluripotent Stem Cells Biology Mitochondrion Bioinformatics Article Catalysis Inorganic Chemistry Transcriptome lcsh:Chemistry Angelman syndrome Gene expression Gene duplication UBE3A medicine Animals Humans oxidative stress Physical and Theoretical Chemistry Molecular Biology Gene lcsh:QH301-705.5 Cells Cultured Spectroscopy Mice Knockout reactive oxygen species Tumor Necrosis Factor-alpha Gene Expression Profiling Organic Chemistry Computational Biology General Medicine bioinformatics Fibroblasts medicine.disease Computer Science Applications mitochondria MRNA Sequencing machine learning Gene Expression Regulation lcsh:Biology (General) lcsh:QD1-999 gene expression Female Gene Deletion |
| Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 4156, p 4156 (2020) International Journal of Molecular Sciences Volume 21 Issue 11 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | The UBE3A gene encodes the ubiquitin E3-ligase protein, UBE3A, which is implicated in severe neurodevelopmental disorders. Lack of UBE3A expression results in Angelman syndrome, while UBE3A overexpression, due to genomic 15q duplication, results in autism. The cellular roles of UBE3A are not fully understood, yet a growing body of evidence indicates that these disorders involve mitochondrial dysfunction and increased oxidative stress. We utilized bioinformatics approaches to delineate the effects of murine Ube3a deletion on the expression of mitochondrial-related genes and pathways. For this, we generated an mRNA sequencing dataset from mouse embryonic fibroblasts (MEFs) in which both alleles of Ube3a gene were deleted and their 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 these two genotypes using TNF&alpha application. Transcriptomes of the four groups of MEFs, Ube3a+/+ and Ube3a&minus /&minus with or without the application of TNF&alpha were analyzed using various bioinformatics tools and machine learning approaches. Our results indicate that Ube3a deletion affects the gene expression profiles of mitochondrial-associated pathways. We further confirmed these results by analyzing other publicly available human transcriptome datasets of Angelman syndrome and 15q duplication syndrome. |
| Databáze: | OpenAIRE |
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