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Splicing factors SRSF1 and SRSF2 regulation of MDM2 alternative splicing is conserved in mice and humans

We have developed a damage-inducible mouse minigene, Mdm2 3-11-12s that recapitulates the splicing of the human MDM2 as well as the mouse endogenous gene by excluding its intervening exon under genotoxic stress (UV-C light). By using site-directed mutagenesis and the CRISPR-Cas9 technology, we generated mutations for the predicted SRSF1 and SRSF2 binding sites, to assess changes in alternative splicing. In the present work we report that regulation of Mdm2 by both SRSF1 and SRSF2 is conserved in humans and mice and that targeting their binding sites might be a mechanism to change p53 activity in specific cancer types.