Characterization of the 5′ and 3′ untranslated regions in murine mdm2 mRNAs

Abstract

The murine double minute 2 ( mdm2) gene is essential for embryogenesis in mice that express the p53 tumor suppressor protein. Mdm2 levels must be regulated tightly because overexpression of mdm2 contributes to tumorigenesis. We investigated whether the 5′ and 3′ untranslated regions (UTRs) of murine mdm2 affect the expression of MDM2 proteins. Induction of mdm2 expression by p53 results in synthesis of an mdm2 mRNA with a short 5′ UTR. The long 5′ UTR increases internal initiation of translation of a minor MDM2 protein, p76 MDM2, without affecting the efficiency of translation of the full-length p90 MDM2. We discovered two alternative 3′ untranslated regions in murine mdm2 mRNA expressed in the testis. The longer 3′ UTR contains a consensus instability element, but mdm2 mRNAs containing the long and short 3′ UTRs have comparable half-lives. The 3′ UTRs do not affect either initiation codon use or translation efficiency. Thus, the murine 5′ UTR, but not the 3′UTR, influences the ratio of the two MDM2 proteins but neither UTR affects MDM2 abundance significantly.