THE TOBACCO ETCH VIRAL 5'-LEADER AND POLY(A) TAIL ARE FUNCTIONALLY SYNERGISTIC REGULATORS OF TRANSLATION

The 5' cap (m(7)GpppN) and the poly(A) tail of eukaryotic mRNAs work in concert to establish an efficient level of translation in vivo. Nevertheless, several mRNAs naturally lack a cap or a poly(A) tail. Determining how these messages effectively compete for the translational machinery not only reveals alternative mechanisms for translational competence, but can also underscore similarities between alternative mechanisms and the standard cap/poly(A) tail interaction. The genomic RNA of tobacco etch virus (TEV), a potyvirus, is a polyadenylated mRNA that naturally lacks a cap (m(7)GpppN) at the 5'-terminus and yet is a highly competitive mRNA during translation. The 144-nt 5'-leader is largely responsible for directing efficient translation and can greatly increase the translational competence of reporter mRNAs. We have examined the synergy between the TEV 5'-leader and the poly(A) tail in transfected plant and animal cells. The TEV 5'-leader functioned optimally as a regulator of reporter mRNA translation only when a poly(A) tail was present. The effect of the TEV 5'-leader on the translation of capped transcripts was significantly less than that for uncapped mRNAs, suggesting that the TEV 5'-leader and the cap may promote similar steps in translation.