Dual tRNA mimicry in the Cricket Paralysis Virus IRES uncovers an unexpected similarity with the Hepatitis C Virus IRES

Abstract

Co-opting the cellular machinery for protein production is a compulsory requirement for viruses. The Cricket Paralysis virus employs an Internal Ribosomal Entry Site (IRES) to express its structural genes in the late stage of infection. Ribosome hijacking is achieved by a sophisticated use of molecular mimicry to tRNA and mRNA, employed to manipulate intrinsically dynamic components of the ribosome. Binding and translocation through the ribosome is required for this IRES to initiate translation. We report two structures, solved by single particle electron cryomicroscopy (cryoEM), of a double translocated CrPV IRES with aminoacyl-tRNA in the peptidyl site (P site) of the ribosome. CrPV IRES adopts a previously unseen conformation, mimicking the acceptor stem of a canonical E site tRNA. The structures suggest a mechanism for the positioning of the first aminoacyl-tRNA shared with the distantly related Hepatitis C Virus IRES.