{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T04:36:07Z","timestamp":1769056567847,"version":"3.49.0"},"reference-count":46,"publisher":"Society for Neuroscience","issue":"39","license":[{"start":{"date-parts":[[2013,3,26]],"date-time":"2013-03-26T00:00:00Z","timestamp":1364256000000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2012,9,26]]},"abstract":"<jats:p>The<jats:italic>bcl-x<\/jats:italic>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<jats:sub>L<\/jats:sub>(the long form) is anti-apoptotic, while Bcl-x<jats:sub>S<\/jats:sub>(short form) is pro-apoptotic. Despite the antagonistic activities of these two isoforms, little is known about how regulation of alternative splicing of<jats:italic>bcl-x<\/jats:italic>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<jats:sub>L<\/jats:sub>while increasing Bcl-x<jats:sub>S<\/jats:sub>. Specific knockdown of Bcl-x<jats:sub>S<\/jats:sub>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<jats:sub>L<\/jats:sub>5\u2032 splice site, altering the Bcl-x<jats:sub>L<\/jats:sub>\/Bcl-x<jats:sub>S<\/jats:sub>ratio and influencing cell death.<jats:italic>In vivo<\/jats:italic>, neonatal hypoxia\u2013ischemia reciprocally altered Bcl-x pre-mRNA splicing, similar to the<jats:italic>in vitro<\/jats:italic>studies. Manipulation of the splice isoforms using viral gene transfer of Bcl-x<jats:sub>S<\/jats:sub>shRNA into the hippocampus of rats before neonatal hypoxia\u2013ischemia 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.<\/jats:p>","DOI":"10.1523\/jneurosci.2617-12.2012","type":"journal-article","created":{"date-parts":[[2012,9,27]],"date-time":"2012-09-27T07:04:43Z","timestamp":1348729483000},"page":"13587-13596","source":"Crossref","is-referenced-by-count":18,"title":["Bcl-x Pre-mRNA Splicing Regulates Brain Injury after Neonatal Hypoxia-Ischemia"],"prefix":"10.1523","volume":"32","author":[{"given":"Qingli","family":"Xiao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andria 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