Viral internal ribosomal entry sites: four classes for one goal

Abstract

To ensure efficient propagation, viruses need to rapidly produce viral proteins after cell entrance. Since viral genomes do not encode any components of the protein biosynthesis machinery, viral proteins must be produced by the host cell. To hi-jack the host cellular translation, viruses use a great variety of distinct strategies. Many single-stranded positive-sensed RNA viruses contain so-called internal ribosome entry sites (IRESs). IRESs are structural RNA motifs that have evolved to specific folds that recruit the host ribosomes on the viral coding sequences in order to synthesize viral proteins. In host canonical translation, recruitment of the translation machinery components is essentially guided by the 5' cap (m G) of mRNA. In contrast, IRESs are able to promote efficient ribosome assembly internally and in cap-independent manner. IRESs have been categorized into four classes, based on their length, nucleotide sequence, secondary and tertiary structures, as well as their mode of action. Classes I and II require the assistance of cellular auxiliary factors, the eukaryotic intiation factors (eIF), for efficient ribosome assembly. Class III IRESs require only a subset of eIFs whereas Class IV, which are the more compact, can promote translation without any eIFs. Extensive functional and structural investigations of IRESs over the past decades have allowed a better understanding of their mode of action for viral translation. Because viral translation has a pivotal role in the infectious program, IRESs are therefore attractive targets for therapeutic purposes. WIREs RNA 2018, 9:e1458. doi: 10.1002/wrna.1458 This article is categorized under: Translation > Ribosome Structure/Function Translation > Translation Mechanisms RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.

A broad-spectrum antiviral molecule, QL47, selectively inhibits eukaryotic translation

“…Although flaviviruses, including DV, have a 5Ј cap and initiate translation primarily via a canonical mechanism (11,14,16), many other RNA viruses have evolved strategies to initiate translation via mechanisms that do not require all factors of the canonical pathway. Notably, many viruses utilize IRES for direct recruitment of host ribosomes and eIFs to viral RNA and initiation of translation via cap-independent mechanisms (29). These IRES elements have been grouped into four distinct classes based on their mode of translation initiation (29).…”

“…Notably, many viruses utilize IRES for direct recruitment of host ribosomes and eIFs to viral RNA and initiation of translation via cap-independent mechanisms (29). These IRES elements have been grouped into four distinct classes based on their mode of translation initiation (29). Members of classes I and II require all host translation initiation factors except for eIF4E, and class II IRES initiate translation at a start codon without ribosomal scanning.…”

The Human Fragile X Mental Retardation Protein Inhibits the Elongation Step of Translation through its RGG and C-terminal domains

“…Therefore, we sought to test hFMRP inhibition of canonical capped-and-tailed RLuc mRNA against internal ribosome entry site (IRES)driven mRNAs. We generated RLuc mRNAs driven by a representative IRES from the four different classes of IRESes: poliovirus (PV-RLuc), encephalomyocarditis virus (EMCV-RLuc), hepatitis C virus (HCV-RLuc), and cricket paralysis virus (CrPV-RLuc) [49]. Unfortunately, the PV-RLuc and HCV-RLuc mRNAs did not translate efficiently enough for IVT studies, so we proceeded with the EMCV-RLuc and CrPV-RLuc mRNAs at a fixed 10 nanomolar concentration for comparison against 10 nanomolar canonical RLuc (Figure 3a).…”

RNA mimicry in post‐transcriptional regulation by aminoacyl tRNA synthetases

“…GlyRS : Many viruses utilize internal ribosome entry site (IRES) to induce their translation once inside the host (Mailliot & Martin, ). This mechanism allows a cap‐independent translation process, and therefore the viral translation is resistant to translation inhibition that affects the host machinery.…”

“…This leads to association of the elongation factor EF1A and enhances translation through the 5 0 end of the mRNA. (d) HisRS binds an anticodon like element within its open reading frame (ORF) and represses translation GlyRS: Many viruses utilize internal ribosome entry site (IRES) to induce their translation once inside the host (Mailliot & Martin, 2018). This mechanism allows a cap-independent translation process, and therefore the viral translation is resistant to translation inhibition that affects the host machinery.…”