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

The murine double minute 2 (mdm2) gene is essential for embryogenesis in mi ce that express the p53 tumor suppressor protein. Mdm2 levels must be regul ated tightly because overexpression of mdm2 contributes to tumorigenesis. W e investigated whether the 5' and 3' untranslated regions (UTRs) of murine mdm2 affect the expression of MDM2 proteins. Induction of mdm2 expression b y 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-leng th p90(MDM2). We discovered two alternative 3' untranslated regions in muri ne mdm2 mRNA expressed in the testis. The longer 3' UTR contains a consensu s instability element: but mdm2 mRNAs containing the long and short 3' UTRs have comparable half-lives. The 3' UTRs do not affect either initiation co don use or translation efficiency. Thus, the murine 5' UTR, but not the 3'U TR, influences the ratio of the two MDM2 proteins but neither UTR affects M DM2 abundance significantly. (C) 2001 Elsevier Science B,V. All rights rese rved.