Characterization of the 5' and 3' untranslated regions in murine mdm2 mRNAs.
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.
Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, WI, Madison, USA.
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Mendrysa
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McElwee
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Perry
D020413:3' Untranslated Regions / Q000235:genetics*; D020121:5' Untranslated Regions / Q000235:genetics*; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D019556:COS Cells; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000235:genetics; D018900:Dinucleotide Repeats / Q000235:genetics; D005091:Exons / Q000235:genetics; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009115:Muridae; D009687:Nuclear Proteins; D011061:Poly A / Q000235:genetics; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D014018:Tissue Distribution
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011061:Poly A; D004247:DNA; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2