Short and Sweet: Viral 5`-UTR as a Canonical and Non-Canonical Translation Initiation Switch

Figures

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  Figure 1:. Canonical and non-canonical mechanisms of translation initiation. (A) Schematic representation of canonical or cap-dependent translation initiation. Translation initiation factors eIF1, eIF1A, eIF2, eIF3, eIF5, eIF4E, eIF4A, eIF4B, eIF4G are labeled as numbers. Small ribosomal subunit is marked as 40S. The 43S PIC (40S, eIF1, eIF1A, eIF3, eIF5, and eIF2•GTP•Met-tRNAiMet) is recruited to the 5’-end of mRNA via the cap-binding protein eIF4E bound to m7G-cap (red circle), and RNA helicase eIF4A is recruited to the scaffold protein eIF4G. (B) IRES-mediated translation initiation. Ribosomes are recruited internally (downstream of 5’-end) to mRNA and positioned adjacent to or on the initiation codon. IRES is represented as a complex secondary RNA structure. (C) CITE-directed translation. Translation machinery is recruited by eIF4G to the extreme 5’-end of the mRNA independently of capping. CITEs utilize 5’-end scanning similar to canonical translation but unlike IRES-mediated translation initiation mechanism. (B and C) Cap-binding factor eIF4E does not participate in IRES- and CITE-mediated translation initiation mechanisms.

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  Figure 2:. Translation initiation switch model for black beetle virus RNA1 5′-UTR CITE. During early stages of infection (A), both black beetle virus (BBV) RNAs (RNA1 is shown in red, RNA2 is shown in blue) are translated via canonical cap-dependent translation initiation mechanism, in which the RNA1 5′-UTR CITE element functions as a Kozak sequence to enhance start codon selection. In later stages of BBV infection (B), cap-dependent translation is downregulated due to stress induced, in part, by disruption of mitochondrial and ER membranes for virion packaging and accompanying release of reactive oxygen species (ROS). Under these conditions, BBV RNA1 5′-UTR CITE activity is switched to operate in cap-independent translation initiation.