Removal of an mRNA destabilizing element correlates with the increased oncogenicity of proto-oncogene fos

Abstract

AU-sequence motifs present in the 3' untranslated region (UTR) of many rapidly inducible messenger RNAs have been proposed to mediate their selective degradation. We have analyzed by quantitative nuclease S1 analysis the mRNA decay-rates of viral (v)/c-fos deletion mutants following transfection in a transient assay system. A 67 nucleotide mRNA destabilizing element, encompassing three conserved AUUUA motifs, was identified in the c-fos 3' UTR. The transforming ability of several v/c-fos recombinants correlates with the removal of the AU-rich sequence. Insertion of a c-fos DNA fragment containing the destabilizing element into the alpha-globin 3' UTR confers high instability to the otherwise stable alpha-globin mRNA. We conclude that a major parameter of oncogenicity by the c-fos gene is predicated by the presence or absence of AT-rich sequences located in the 3' non-coding region.