Switch from Cap- to Factorless IRES-Dependent 0 and +1 Frame Translation during Cellular Stress and Dicistrovirus Infection

Wang, Qing S.; Jan, Eric

Among them, the intergenic region IRES (IGR IRES) of the Dicistroviridae family utilizes one of the most unique mechanism to initiate translation. Dicistroviruses possess a single-strand positive sense RNA genome, which contains two open reading frames encoding the structural and nonstructural proteins, each of which is driven by a distinct IRES ( Figure 1A ) [8] [9] [10] . Members of the Dicistroviridae family infect arthropods including Drosophilidae, Aphidoidea, Caridea, and Apidae and include the cricket paralysis virus (CrPV), Drosophila C virus (DCV), and the honey bee viruses such as the Israeli acute paralysis virus (IAPV), acute bee paralysis virus (ABPV), and Kashmir bee virus (KBV) [8] . The intergenic region IRES (IGR IRES) of the Dicistroviridae family adopts a unique triple-pseudoknot RNA structure ( Figure 1B ) to direct ribosome recruitment without the need of initiation factors [11] [12] [13] [14] [15] [16] [17] . Moreover, structural and biochemical studies have revealed that the IRES functionally mimics a tRNA to hijack and manipulate the ribosome [17] [18] [19] . Pseudoknots II and III (PKII and PKIII) compose one domain which binds to 80S, whereas the tRNA-like PKI domain occupies the ribosomal P-site and directs translational initiation from a non-AUG codon in the ribosomal A-site ( Figure 1B) [11, 12, 15, [17] [18] [19] [20] . Recent cryo-EM structures of IGR IRES/ribosome complexes have provided additional insights into this mechanism: the PKI domain first occupies the ribosomal A site and translocation of the IRES by eEF2 occurs prior to delivery of the first aminoacyl-tRNA [21, 22] .