Sequence elements that can function as internal
ribosome entry sites (IRES) have been identified in 5′
noncoding regions of certain uncapped viral and capped
cellular mRNA molecules. However, it has remained largely
unknown whether IRES elements are functional when located
in their natural capped mRNAs. Therefore, the polysomal
association and translation of several IRES-containing
cellular mRNAs was tested under conditions that severely
inhibited cap-dependent translation, that is, after infection
with poliovirus. It was found that several known IRES-containing
mRNAs, such as BiP and c-myc, were both associated with
the translation apparatus and translated in infected cells
when cap-dependent translation of most host-cell mRNAs
was blocked, indicating that the IRES elements were functional
in their natural mRNAs. Curiously, the mRNAs that encode
eukaryotic initiation factor 4GI (eIF4GI) and 4GII (eIF4GII),
two proteins with high identity and similar functions in
the initiation of cap-dependent translation, were both
associated with polysomes in infected cells. The 5′-end
sequences of eIF4GI mRNA were isolated from a cDNA expression
library and shown to function as an internal ribosome entry
site when placed into a dicistronic mRNA. These findings
suggest that eIF4G proteins can be synthesized at times
when 5′ cap-dependent mRNA translation is blocked,
supporting the notion that eIF4G proteins are needed in
both 5′ cap-independent and 5′ cap-dependent
translational initiation mechanisms.