BCAS2 participates in splicing reactions of MDM4 pre-mRNA in HSCs and influences splice site selection.8 In the presence of wild-type levels of BCAS2, the spliceosome preferentially produces MDM4-FL mRNA, which includes exon 6. This results in production of normal MDM4 protein that binds to and inactivates p53. In contrast, in the absence of BCAS2, MDM4 preferentially undergoes alternative spicing, resulting in a shortened version (MDM4-S) that skips exon 6. In BCAS2-null zebrafish, expression of MDM4-S mRNA is increased but MDM4-FL is decreased. The MDM4-S has a premature stop codon, encoding a truncated MDM4-S protein. Together with decreased MDM4-FL mRNA, this results in decreased functional MDM4 protein. Without MDM4 to inactivate it, p53 expression increases leading to increased apoptosis of HSCs.