A mechanism for translationally coupled mRNA turnover: Interaction betweenthe poly(A) tail and a c-fos RNA coding determinant via a protein complex

mRNA turnover mediated by the major protein-coding-region determinant of in stability (mCRD) of the c-fos proto-oncogene transcript illustrates a funct ional interplay between mRNA turnover and translation. We show that the fun ction of mCRD depends on its distance from the poly(A)tail. Five mCRD-assoc iated proteins were identified: Unr, a purine-rich RNA binding protein; PAB P, a poly(A) binding protein; PAIP-1, a poly(A) binding protein interacting protein; hnRNP D, an AU-rich element binding protein; and NSAP1, an hnRNP R-like protein. These proteins form a multiprotein complex. Overexpression of these proteins stabilized mCRD-containing mRNA by impeding deadenylation . We propose that a bridging complex forms between the poly(A) tail and the mCRD and ribosome transit disrupts or reorganizes the complex, leading to rapid RNA deadenylation and decay.