Post-transcriptional regulation by the exosome complex is required for cell survival and forebrain development via repression of P53 signaling
| Autor: | Linh Pham, Godwin Sokpor, Uttiya Basu, Orr Shomroni, Yuanbin Xie, Tea Berulava, Jochen F. Staiger, Joachim Rosenbusch, Tran Tuoc, Huu Phuc Nguyen, Pauline Antonie Ulmke, Andre Fischer |
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| Rok vydání: | 2021 |
| Předmět: |
Exosome complex
RNA Stability genetics [Tumor Suppressor Protein p53] Apoptosis Exosomes RNA decay Mice 0302 clinical medicine pathology [Prosencephalon] metabolism [Exosomes] Gene expression growth & development [Prosencephalon] PUMA protein mouse 0303 health sciences Exosome Multienzyme Ribonuclease Complex Gene Expression Regulation Developmental Stem Cells and Regeneration Cell biology metabolism [RNA] Signal Transduction Cell Survival physiology [Cell Survival] Mice Transgenic Biology genetics [Signal Transduction] genetics [Exosomes] 03 medical and health sciences Prosencephalon ddc:570 Animals Humans Molecular Biology Gene Post-transcriptional regulation 030304 developmental biology genetics [Exosome Multienzyme Ribonuclease Complex] Cortical development Tumor Suppressor Proteins Computational Biology RNA Mice Inbred C57BL metabolism [Exosome Multienzyme Ribonuclease Complex] genetics [Exoribonucleases] P53 pathway Aen and Bbc3 Exosc10 Exoribonucleases Forebrain metabolism [Tumor Suppressor Protein p53] Tumor Suppressor Protein p53 Apoptosis Regulatory Proteins 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Development Development |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.188276 |
| Popis: | Fine-tuned gene expression is crucial for neurodevelopment. The gene expression program is tightly controlled at different levels, including RNA decay. N6-methyladenosine (m6A) methylation-mediated degradation of RNA is essential for brain development. However, m6A methylation impacts not only RNA stability, but also other RNA metabolism processes. How RNA decay contributes to brain development is largely unknown. Here, we show that Exosc10, a RNA exonuclease subunit of the RNA exosome complex, is indispensable for forebrain development. We report that cortical cells undergo overt apoptosis, culminating in cortical agenesis upon conditional deletion of Exosc10 in mouse cortex. Mechanistically, Exosc10 directly binds and degrades transcripts of the P53 signaling-related genes, such as Aen and Bbc3. Overall, our findings suggest a crucial role for Exosc10 in suppressing the P53 pathway, in which the rapid turnover of the apoptosis effectors Aen and Bbc3 mRNAs is essential for cell survival and normal cortical histogenesis. |
| Databáze: | OpenAIRE |
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