Two distinct destabilizing elements in the c-fos message trigger deadenylation as a first step in rapid mRNA decay.

The mechanisms by which c-fos mRNA is targeted for decay have been examined. Rapid removal of the poly(A) tail occurs before the transcribed portion of the c-fos message is degraded. Identification of the determinants that mediate c-fos message deadenylation reveals that they coincide directly with previously characterized determinants of c-fos mRNA instability, one in the protein-coding region and the other an AU-rich element (ARE) in the 3'-untranslated region. Insertion of either of these c-fos instability elements into the stable beta-globin message confers the property of rapid deadenylation. Mutation of the ARE indicates that this sequence controls two steps in the process of c-fos mRNA degradation: removal of the poly(A) tail, which does not require intact AUUUA pentanucleotides within the ARE, and subsequent degradation of the transcribed portion of the message, which appears to be dependent on the AUUUA pentanucleotides. These results indicate that structurally distinct instability determinants within the transcribed portion of labile messages can function by promoting rapid removal of the poly(A) tail as a first step in the decay process.