Structural diversity and biological role of the 5’ untranslated regions of picornavirus

Figures

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  Figure 1.. The viral genome structure of poliovirus and the 5’ UTR of poliovirus and FMDV. (a) The diagram of the viral genome structure of poliovirus. The viral genome is covalently linked to a terminal protein termed VPg. After the translation of the single ORF, newly synthesized polyproteins undergo cascade cleavage by viral-encoded proteases to produce capsid and non-structural proteins, including the VP4, VP2, VP3, VP1, 2Apro, 2B, 2C, 3A, 3B, 3C, and 3Dpol. (b) The diagram of the 5’ UTR structure of poliovirus. The 5’ end of the PV genome is covalently linked to the VPg, and the terminal structure at the 5’ end is a cloverleaf structure followed by an IRES element consisting of five domains, including I, II, III, IV, V, and VI. (c) The diagram of the 5’ UTR structure of FMDV. The 5’ end of the FMDV genome is covalently linked to the VPg, and the terminal structure at the 5’ end folds into a large stem-loop called the S fragment. The S fragment is followed by the poly (C) tract, the tandem PK, the Cre, and the IRES consisting of four domains (II, III, IV, and V). Meanwhile, FMDV contains two AUGs and generally utilizes the second AUG.

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  Figure 2.. The process diagram of the eukaryotic cap-dependent translation initiation and viral IRES-dependent translation. (a) The schematic diagram of the eukaryotic canonical Cap-dependent translation initiation. The translation initiation process is divided into the following stages: (i) the formation of the eIF2-GTP-Met-tRNAi ternary complex (not depicted); (ii) the formation of the 43S preinitiation complex through the eIfs (e.g. eIF1, eIF1A, eIF3, and eIF5) together with the ternary complex and 40S subunit; (iii) the activation of mRNA initiation via the binding of eIF4E (cap-binding protein) to the m7G cap. Then, the attachment of the 43S PIC to activated mRNA. Subsequently, the scanning process of the 5’UTR along the direction from 5’ to 3’ of the mRNA by 43S complexes; (iv) the AUG recognition and the formation of 48S initiation complex, while eIF5 mediates the hydrolysis of GTP and release of Pi. (v) the subunit joining of 60S subunits to 48S complexes; (vi) the elongation began with the formation of the 80S ribosome complex and the hydrolysis of eIF5B. (b) The schematic diagram of viral IRES-dependent translation initiation. During the virus infection, the IRES element can…

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  Figure 3.. The diagram of the secondary structure of typical four types of IRES elements in RNA viruses. (a) The structure diagram of type I IRES. Type I IRES consists of five domains, among which domain IV is the functional centre domain. Domain IV has a GNRA motif necessary for IRES activity, indicated by navy blue. Significant motifs are marked by navy blue that can maintain a secondary structure or be recognized by IRES trans-acting factors (ITAFs). G is guanine, N is any nucleotide, R is a purine (A or G), and A is adenine. (b) The structure diagram of type II IRES. Type II IRES consists of four domains, among which domain III plays a crucial role in IRES function. Domain IV has GNRA and RAAA motifs essential for IRES activity, indicated by navy blue. G is guanine, N is any nucleotide, R is a purine (A or G), and A is adenine. (c) The structure diagram of HCV/HCV-like IRES. AUG is the initiation codon, indicated by the yellow colour. (d) The structure diagram of IGR IRES. IGR IRES contains the L1.1, L1.2, PKI, PKII, PK III, SLIV, and SLV structures.