| First Author | Lin L | Year | 2020 |
| Journal | Neuron | Volume | 107 |
| Issue | 6 | Pages | 1180-1196.e8 |
| PubMed ID | 32710818 | Mgi Jnum | J:297779 |
| Mgi Id | MGI:6479257 | Doi | 10.1016/j.neuron.2020.06.036 |
| Citation | Lin L, et al. (2020) Developmental Attenuation of Neuronal Apoptosis by Neural-Specific Splicing of Bak1 Microexon. Neuron 107(6):1180-1196.e8 |
| abstractText | Continuous neuronal survival is vital for mammals because mammalian brains have limited regeneration capability. After neurogenesis, suppression of apoptosis is needed to ensure a neuron's long-term survival. Here we describe a robust genetic program that intrinsically attenuates apoptosis competence in neurons. Developmental downregulation of the splicing regulator PTBP1 in immature neurons allows neural-specific splicing of the evolutionarily conserved Bak1 microexon 5. Exon 5 inclusion triggers nonsense-mediated mRNA decay (NMD) and unproductive translation of Bak1 transcripts (N-Bak mRNA), leading to suppression of pro-apoptotic BAK1 proteins and allowing neurons to reduce apoptosis. Germline heterozygous ablation of exon 5 increases BAK1 proteins exclusively in the brain, inflates neuronal apoptosis, and leads to early postnatal mortality. Therefore, neural-specific exon 5 splicing and depletion of BAK1 proteins uniquely repress neuronal apoptosis. Although apoptosis is important for development, attenuation of apoptosis competence through neural-specific splicing of the Bak1 microexon is essential for neuronal and animal survival. |
