REGULATED POLY(A) TAIL SHORTENING IN SOMATIC-CELLS MEDIATED BY CAP-PROXIMAL TRANSLATIONAL REPRESSOR PROTEINS AND RIBOSOME ASSOCIATION

The poly(A) tail plays an important role in translation initiation. We report the identification of a mechanism that operates in mammalian s omatic cells, and couples mRNA poly(A) tail length with its translatio n state. The regulation of human ferritin L-chain mRNA by iron-respons ive elements (IRPs) and iron regulatory proteins (IRPs) is subject to this mechanism: translational repression imposed by IRP binding to the IRE of ferritin L-chain mRNA induces poly(A) tail shortening. For the accumulation of mRNAs with short poly(A) tails, IRP binding to an IRE per se is not sufficient, but must cause translational repression. In terestingly, puromycin and verrucarin (general translation inhibitors that dissociate mRNAs from ribosomes) mimick the negative effect of th e specific translational repressor proteins on poly(A) tail length, wh ereas cycloheximide and anisomycin (general translation inhibitors tha t maintain the association between mRNAs and ribosomes) preserve long poly(A) tails. Thus, the ribosome association of the mRNA appears to r epresent the critical determinant. These findings identify a novel mec hanism of regulated polyadenylation as a consequence of translational control. They reveal differences in poly(A) tail metabolism between po lysomal and mRNP-associated mRNAs. A possible role of this mechanism i n the maintenance of translational repression is discussed.