Intracellular modifications induced by poliovirus reduce the requirement for structural motifs in the 5' noncoding region of the genome involved in internal initiation of protein synthesis

Abstract

A series of genetic deletions based partly on two RNA secondary structure models (M. A.

Distinctive features of foot-and-mouth disease virus, a member of the picornavirus family; aspects of virus protein synthesis, protein processing and structure

“…However in this case, the open reading frame following this upstream AUG is very short, only three amino acids would bc joined. Surprisingly the presence of the upstream mini-ORF in the type C constructs did not affect the site selection either in the presence or absence of the IRES, probably as a result of the very short ORF following this upstream AUG (Belsham, 1992).…”

“…No evidence has been obtained for the FMDV/cardiovirus IRES that any of the internal stem-loop elements are dispensible for IRES activity. However in PV deletion of one internal stem-loop structure seems not to greatly affect IRES activity (Nicholson et al, 1991;Percy et al, 1992). This particular structure is not present within the 5'NCR of a related enterovirus, namely bovine enterovirus (Earle et al, 1988).…”

“…Although it has become apparent that a complex RNA structure is required for the IRES to function, an unexpected phenomenon has been observed in studies on the PV IRES. Deletion of certain domains within this element completely abolished its ability to direct the translation of the second ORF (CAT) from a bicistronic construct when assayed alone, however when the construct was cotransfected with a full-length PV cDNA, the expression of CAT activity was again observed (Percy et al, 1992). The expression of the full-length PV cDNA clone was accompanied by the inhibition of cap-dependent translation.…”

“…The expression of the full-length PV cDNA clone was accompanied by the inhibition of cap-dependent translation. The enhanced CAT expression was interpreted as suggesting that some of the sequences within the IRES were dispensible within cells in which cap-dependent translation was abolished (Percy et al, 1992). It was presumed that additional initiation factors that would otherwise be utilized by capped transcripts became available.…”

“…In FMDV type O the two initiation sites are separated by 84 bases and both sites are used with similar efficiency. Experiments wcrc performed to examine the selection of the different initiation sites in FMDV under a variety of conditions (Belsham, 1992). It was shown that initiation of protein synthesis occurred at both sites on RNAs containing either just 60 bases upstream of the first initiation site or the complete IRES element.…”