RESUMEN

Picornavirus mRNAs contain IRESs that sustain their translation during infection, when host protein synthesis is shut off. The major classes of picornavirus IRESs (Types 1 and 2) have distinct structures and sequences, but initiation on both is determined by their specific interaction with eIF4G. We report here that Aichivirus (AV), a member of the Kobuvirus genus of Picornaviridae, contains an IRES that differs structurally from Type 1 and Type 2 IRESs. Its function similarly involves interaction with eIF4G, but its eIF4G-interacting domain is structurally distinct, although it contains an apical eIF4G-interacting motif similar to that in Type 2 IRESs. Like Type 1 and Type 2 IRESs, AV IRES function is enhanced by pyrimidine tract-binding protein (PTB), but the pattern of PTB's interaction with each of these IRESs is distinct. Unlike all known IRESs, the AV IRES is absolutely dependent on DHX29, a requirement imposed by sequestration of its initiation codon in a stable hairpin.

Asunto(s)

Kobuvirus/genética , Iniciación de la Cadena Peptídica Traduccional/genética , Picornaviridae/genética , ARN Viral/genética , Elementos Reguladores de la Transcripción/fisiología , Regiones no Traducidas 5'/genética , Secuencia de Bases , Sitios de Unión/genética , Regulación Viral de la Expresión Génica , Modelos Moleculares , Datos de Secuencia Molecular , Conformación de Ácido Nucleico , Picornaviridae/metabolismo , Biosíntesis de Proteínas/genética , Biosíntesis de Proteínas/fisiología , ARN Viral/química , ARN Viral/metabolismo , Elementos Reguladores de la Transcripción/genética , Ribosomas/metabolismo