The 5'-poly(A) leader of poxvirus mRNA confers a translational advantage that can be achieved in cells with impaired cap-dependent translation

The poly(a) leader at the 5’-untranslated region (5’-utr) is an unusually striking feature of all poxvirus mrnas transcribed after viral dna replication (post-replicative mrnas). these poly(a) leaders are non-templated and of heterogeneous lengths; and their function during vacv infection remains a long-standing question. here,we discovered that a 5’-poly(a) leader conferred a selective translational advantage to mrna in poxvirus-infected cells. a constitutive and uninterrupted 5’-poly(a) leader with 12 residues was optimal. because the most frequent lengths of the 5’-poly(a) leaders are 8–12 residues,the result suggests that the poly(a) leader has been evolutionarily optimized to boost vacv protein production. a 5’-poly(a) leader also could increase protein production in the bacteriophage t7 promoter-based vaccinia virus expression system,the prototypic member of poxviruses. interestingly,although vaccinia virus post-replicative mrnas do have 5’- methylated guanosine caps and can use cap-dependent translation,in vaccinia virus-infected cells,mrna with a 5’-poly(a) leader could also be efficiently translated in cells with impaired cap-dependent translation. however,the translation was not mediated through an internal ribosome entry site (ires). these results point to a fundamental mechanism poxvirus uses to efficiently translate its post-replicative mrnas. © 2017 dhungel et al.