ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Bcl-x pre-mRNA splicing regulates brain injury after neonatal hypoxia-ischemia.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 24 citations in OpenAlex.
- Global analysis of excitotoxicity-induced alterations in RNA structure and RNA-protein binding in neurons.iScience · 2025Article
- Truncated Dyrk1A aggravates neuronal apoptosis by inhibiting ASF-mediated Bcl-x exon 2b inclusion.CNS neuroscience & therapeutics · 2024Article
- The alternative 3' splice site ofIbrain · 2022Article
- Hypoxia-induced alternative splicing in human diseases: the pledge, the turn, and the prestige.Cellular and molecular life sciences : CMLS · 2021Review
- Proteome profiling of different rat brain regions reveals the modulatory effect of prolonged maternal separation on proteins involved in cell death-related processes.Biological research · 2021Article
- Oxidative stress battles neuronal Bcl-xL in a fight to the death.Neural regeneration research · 2021Article
- Hypoxia-induced alternative splicing: the 11th Hallmark of Cancer.Journal of experimental & clinical cancer research : CR · 2020Review
- RNA Binding Motif 5 (RBM5) in the CNS-Moving Beyond Cancer to Harness RNA Splicing to Mitigate the Consequences of Brain Injury.Frontiers in molecular neuroscience · 2020Article
- Subacute to chronic Alzheimer-like alterations after controlled cortical impact in human tau transgenic mice.Scientific reports · 2019Article
- Bestrophin-3 Expression in a Subpopulation of Astrocytes in the Neonatal Brain After Hypoxic-Ischemic Injury.Frontiers in physiology · 2019Article
- Post-Transcriptional Regulation of Anti-Apoptotic BCL2 Family Members.International journal of molecular sciences · 2018Review
- NG25, an inhibitor of transforming growth factor‑β‑activated kinase 1, ameliorates neuronal apoptosis in neonatal hypoxic‑ischemic rats.Molecular medicine reports · 2018Article
- Group VIA Phospholipase A2 (iPLA2β) Modulates Bcl-x 5'-Splice Site Selection and Suppresses Anti-apoptotic Bcl-x(L) in β-Cells.The Journal of biological chemistry · 2015Article
- In vitro analysis of splice site mutations in the CLCN1 gene using the minigene assay.Molecular biology reports · 2014Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The bcl-x gene appears to play a critical role in regulating apoptosis in the developing and mature CNS and following CNS injury. Two isoforms of Bcl-x are produced as a result of alternative pre-mRNA splicing: Bcl-x(L) (the long form) is anti-apoptotic, while Bcl-x(S) (short form) is pro-apoptotic. Despite the antagonistic activities of these two isoforms, little is known about how regulation of alternative splicing of bcl-x may mediate neural cell apoptosis. Here, we report that apoptotic stimuli (staurosporine or C2-ceramide) reciprocally altered Bcl-x splicing in neural cells, decreasing Bcl-x(L) while increasing Bcl-x(S). Specific knockdown of Bcl-x(S) attenuated apoptosis. To further define regulatory elements that influenced Bcl-x splicing, a Bcl-x minigene was constructed. Deletional analysis revealed several consensus sequences within intron 2 that altered splicing. We found that the splicing factor, CUG-binding-protein-1 (CUGBP1), bound to a consensus sequence close to the Bcl-x(L) 5' splice site, altering the Bcl-x(L)/Bcl-x(S) ratio and influencing cell death. In vivo, neonatal hypoxia-ischemia reciprocally altered Bcl-x pre-mRNA splicing, similar to the in vitro studies. Manipulation of the splice isoforms using viral gene transfer of Bcl-x(S) shRNA into the hippocampus of rats before neonatal hypoxia-ischemia decreased vulnerability to injury. Moreover, alterations in nuclear CUGBP1 preceded Bcl-x splicing changes. These results suggest that alternative pre-mRNA splicing may be an important regulatory mechanism for cell death after acute neurological injury and may potentially provide novel targets for intervention.
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