tRNA-mimicry in IRES-mediated translation and recoding

Abstract

Viruses maintain compact genomes that must be packaged within capsids typically less than 200 nanometers in diameter. Therefore, instead of coding for a full set of genes needed for replication, viruses have evolved remarkable strategies for co-opting the host cellular machinery. Additionally, viruses often increase the coding capacity of their own genomes by employing overlapping open reading frames (ORFs). Some overlapping viral ORFs involve recoding events that are programmed by the viral RNA. During these programmed recoding events, the ribosome is directed to translate in an alternative reading frame. Here we describe how the Dicistroviridae family of viruses utilize an internal ribosome entry site (IRES) in order to recruit ribosomes to initiate translation at a non-AUG codon. The IRES accomplishes this in part by mimicking the structure of a tRNA. Recently, we showed that the Israeli Acute Paralysis Virus (IAPV) member of the Dicistroviridae family utilizes its IRES to initiate translation in 2 different reading frames. Thus, IAPV has evolved an apparently novel recoding mechanism that reveals important insights into translation. Finally, we compare the IAPV structure to other systems that utilize tRNA mimicry in translation.