Caspase-9 messenger RNA (CASP9 mRNA)

Caspase-9 messenger RNA (CASP9 mRNA) is the transcript of the CASP9 gene, which encodes a critical initiator protease in the intrinsic (mitochondrial) apoptotic pathway. Upon cellular stress, the resulting Caspase-9 protein is activated within the apoptosome complex, subsequently triggering executioner caspases like Caspase-3 to carry out programmed cell death (UniProt P55211). The CASP9 mRNA is subject to alternative splicing, producing two primary isoforms: the full-length pro-apoptotic CASP9a and the truncated anti-apoptotic CASP9b, which lacks the catalytic domain (PubMed 25665524). In many cancers, the splicing machinery is dysregulated to favor CASP9b, allowing cells to evade apoptosis and survive under stress. Conversely, in neurodegenerative diseases, excessive CASP9a activity can contribute to premature neuronal loss (PubMed 18463610). Therapeutic strategies targeting CASP9 mRNA include antisense oligonucleotides (ASOs) and splice-switching oligonucleotides (SSOs) designed to shift the isoform balance or siRNAs intended to silence expression, providing a precise mechanism to modulate the apoptotic threshold in diseased tissues (NCBI Gene 842).

Other names

Caspase-9 mRNAMCH6 mRNAICE-LAP6 mRNAAPAF-3 mRNAApoptotic protease-activating factor 3 mRNA

Modulation of alternative splicing to alter the ratio of pro-apoptotic (CASP9a) to anti-apoptotic (CASP9b) isoforms, or RNA interference-mediated degradation to reduce total protein expression.