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Foot-and-mouth disease virus (FMDV) and other picornaviruses initiate translation of their positive-strand RNA genomes at the highly structured internal ribosome entry site (IRES), which mediates ribosome recruitment to an internal site of the virus RNA. This process is facilitated by eukaryotic translation initiation factors (eIFs), such as eIF4G and eIF4B. In the eIF4G-binding site, a characteristic, discontinuous sequence element is highly conserved within the cardio- and aphthovirus subgroup (including FMDV) of the picornaviruses. This conserved element was mutated in order to investigate its primary sequence and secondary structure requirements for IRES function. Both binding of eIF4G to the IRES and IRES-directed translation are seriously impaired by mutations in two unpaired dinucleotide stretches that are exposed from the double-stranded (ds)RNA. In the base-paired regions of the conserved element, maintenance of the double-stranded secondary structure is essential, whilst in some cases, the primary sequence within the dsRNA regions is also important for IRES function. Extra eIF4F added to the translation reaction does not restore full IRES activity or eIF4G binding, indicating that disturbances in the structure of this conserved element cannot be overcome by increased initiation factor concentrations.

Original publication

DOI

10.1099/vir.0.80106-0

Type

Journal article

Journal

J Gen Virol

Publication Date

09/2004

Volume

85

Pages

2555 - 2565

Keywords

Animals, Base Sequence, Cell Line, Conserved Sequence, Cricetinae, Eukaryotic Initiation Factor-4F, Foot-and-Mouth Disease Virus, Genome, Viral, Molecular Sequence Data, Mutation, Nucleic Acid Conformation, Protein Binding, Ribosomes, Virus Replication