What determines the instability of c-myc proto-oncogene mRNA?

Abstract

The c-myc proto-oncogene is believed to be involved in the regulation of cell growth and differentiation. Deregulation of this gene, resulting in an inappropriate increase of gene product, can contribute to cancer formation. One of the ways in which the expression of the c-myc gene can be deregulated is by the stabilization of the labile c-myc mRNA. The rapid degradation of the c-myc transcript appears to be mediated by at least two distinct regions in the mRNA. One lies in the 3' untranslated region, and presumably consists of (A+U)-rich sequences. The other lies in the C-terminal part of the coding region and colocalizes with sequences encoding protein-dimerization motifs. The exact mechanism by which the destabilizing elements function is not yet clear. Shortening of the poly(A) tail of the c-myc message appears to precede degradation of the transcript. When translation is blocked, this shortening is slowed down and the mRNA is stabilized. This suggests that deadenylation is required before degradation of the mRNA body can take place.