31 Translation Initiation on Picornavirus RNA

Abstract

The animal picornaviruses are a large family of viruses which is currently subdivided into six genera (Table 1). They are non-enveloped viruses with a positive-strand RNA genome some 8000 nucleotides in length. Replication occurs entirely within the cytoplasm, as witnessed by the fact that they can replicate efficiently in enucleated cells (Follett et al. 1975). There is a 3′ poly(A) tail that is encoded rather than being added in a template-independent process by a poly(A) polymerase. At the 5′ end there is a covalently linked small virus-encoded protein, VPg (also known as 3B). It is believed that soon after entry into the infected cell, this protein is cleaved off by cellular activities, so that the RNA is effectively translated as an uncapped mRNA. Certainly, VPg is not essential for infectivity, since full length in vitro synthesized RNA (without VPg) is infectious. There is a single open reading frame coding for a polyprotein (Fig. 1), which is rapidly processed to give the individual capsid proteins and viral nonstructural proteins.

The common features of picornavirus 5′-untranslated regions (UTRs) are that they are very long (610 to >1200 nucleotides depending on the species); they have numerous AUG triplets, most of which are not conserved even between different isolates of the same virus (Pöyry et al. 1992); and they are predicted to fold into complex secondary structures. These characteristics, together with the fact that the RNA is not capped, imply that the RNAs cannot possibly be translated efficiently by the conventional scanning mechanism. Initiation...