Entrapping Ribosomes for Viral Translation: tRNA Mimicry as a Molecular Trojan Horse

Abstract Turnip yellow mosaic virus (TYMV) has a genomic plus-strand RNA with a 5′ cap followed by overlapping and different reading frames for the movement protein and polyprotein, while the distal coat protein cistron is translated from a subgenomic RNA. The 3′-untranslated region harbors a tRNA-like structure (TLS) to which a valine moiety can be added and it is indispensable for virus viability. Here, we report about a surprising interaction between TYMV-RNA-programmed ribosomes and 3′-valylated TLS that yields polyprotein with the valine N terminally incorporated by a translation mechanism resistant to regular initiation inhibitors. Disruption of the TLS exclusively abolishes polyprotein synthesis, which can be restored by adding excess TLS in trans . Our observations imply a novel eukaryotic mechanism for internal initiation of mRNA translation.