%0 Journal Article
%T The 5'-poly(A) leader of poxvirus mRNA confers a translational advantage that can be achieved in cells with impaired cap-dependent translation
%A Pragyesh Dhungel
%A Shuai Cao
%A Zhilong Yang
%J -
%D 2017
%R 10.1371/journal.ppat.1006602
%X 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 poxvirus 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¨C12 residues, the result suggests that the poly(A) leader has been evolutionarily optimized to boost poxvirus protein production. A 5¡¯-poly(A) leader also could increase protein production in the bacteriophage T7 promoter-based expression system of vaccinia virus, 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
%K Messenger RNA
%K Protein translation
%K Luciferase
%K HeLa cells
%K Transfection
%K Gene expression
%K Internal ribosome entry site
%K Small interfering RNAs
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006602