UBE3A regulates the transcription of IRF, an antiviral immunity
| Autor: | Ryohei Furumai, Xiaoxi Liu, Kota Tamada, Toru Takumi |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Cytoplasm
congenital hereditary and neonatal diseases and abnormalities Ubiquitin-Protein Ligases Mice Transgenic Antiviral Agents Transcriptome Mice 03 medical and health sciences Intellectual Disability Angelman syndrome Genetics UBE3A Transcriptional regulation medicine Animals Humans Molecular Biology Genetics (clinical) Cell Nucleus Neurons 0303 health sciences biology 030305 genetics & heredity Immunity Brain General Medicine medicine.disease Cell biology Ubiquitin ligase Disease Models Animal Cell nucleus HEK293 Cells medicine.anatomical_structure Gene Expression Regulation Nuclear receptor biology.protein General Article Angelman Syndrome Interferon Regulatory Factor-2 Interferon Regulatory Factor-1 Interferon regulatory factors |
| Zdroj: | Hum Mol Genet |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/ddz019 |
| Popis: | UBE3A is a gene responsible for the pathogenesis of Angelman syndrome (AS), a neurodevelopmental disorder characterized by symptoms such as intellectual disability, delayed development and severe speech impairment. UBE3A encodes an E3 ubiquitin ligase, for which several targets have been identified, including synaptic molecules. Although proteolysis mainly occurs in the cytoplasm, UBE3A is localized to the cytoplasm and the nucleus. In fact, UBE3A is also known as a transcriptional regulator of the family of nuclear receptors. However, the function of UBE3A in the nucleus remains unclear. Therefore, we examined the involvement of UBE3A in transcription in the nuclei of neurons. Genome-wide transcriptome analysis revealed an enrichment of genes downstream of interferon regulatory factor (IRF) in a UBE3A-deficient AS mouse model. In vitro biochemical analyses further demonstrated that UBE3A interacted with IRF and, more importantly, that UBE3A enhanced IRF-dependent transcription. These results suggest a function for UBE3A as a transcriptional regulator of the immune system in the brain. These findings also provide informative molecular insights into the function of UBE3A in the brain and in AS pathogenesis. |
| Databáze: | OpenAIRE |
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