Poxvirus-encoded decapping enzymes promote selective translation of viral mRNAs.

ABSTRACT: Cellular decapping enzymes negatively regulate gene expression by removing the methylguanosine cap at the 5' end of eukaryotic mRNA, rendering mRNA susceptible to degradation and repressing mRNA translation. Vaccinia virus (VACV), the prototype poxvirus, encodes two decapping enzymes, D9 and D10, that induce the degradation of both cellular and viral mRNAs. Using a genome-wide survey of translation efficiency, we analyzed vaccinia virus mRNAs in cells infected with wild type VACV and mutant VACVs with inactivated decapping enzymes. We found that VACV decapping enzymes are required for selective translation of viral post-replicative mRNAs (transcribed after viral DNA replication) independent of PKR- and RNase L-mediated translation repression. Further molecular characterization demonstrated that VACV decapping enzymes are necessary for efficient translation of mRNA with a 5'-poly(A) leader, which are present in all viral post-replicative mRNAs. Inactivation of D10 alone in VACV significantly impairs poly(A)-leader-mediated translation. Remarkably, D10 stimulates mRNA translation in the absence of VACV infection with a preference for RNA containing a 5'-poly(A) leader. We further revealed that VACV decapping enzymes are needed for 5'-poly(A) leader-mediated cap-independent translation enhancement during infection. Our findings identified a mechanism by which VACV mRNAs are selectively translated through subverting viral decapping enzymes to stimulate 5'-poly(A) leader-mediated translation.

SUBMITTER: Cantu F 

PROVIDER: S-EPMC7575113 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature