Switch from Cap- to Factorless IRES-Dependent 0 and +1 Frame Translation during Cellular Stress and Dicistrovirus Infection

Wang, Qing S.; Jan, Eric

The majority of eukaryotic mRNAs utilize a cap-dependent scanning mechanism to recruit the ribosome, whereas internal ribosome entry sites are cis-acting elements that direct recruitment of the ribosome in a 59 end independent manner. Initially discovered in picornaviruses, IRESs have been found in other viruses including flaviviruses, retroviruses, and dicistroviruses and in a subset of cellular mRNAs [1, 2] . IRESs, in general, adopt RNA structures that recruit specific translation initiation factors or IRES trans-acting factors (ITAFs) that contribute to ribosome recruitment and translation initiation [3, 4] . In general, within each viral family, the factor requirements for IRES translation are unique [5] which likely reflects the mechanism by which translation is inhibited during virus infection. For example in poliovirus infection, the viral protease targets not only the viral polyprotein but also translation initiation factors, eIF4G and PABP, resulting in the shutoff of host translation. In contrast, the polioviral IRES can still utilize the cleaved C-terminal fragment of eIF4G to mediate viral protein translation [6] . It is proposed that the IRES allows for preferential translation of an mRNA during cellular stress or viral infection when overall cap-dependent translation is compromised [1, 7] . Coordination of this switch from cap-dependent translation to IRES-dependent translation is an important strategy utilized by some positive strand RNA viruses to efficiently hijack the ribosome for productive viral protein synthesis [1, 7] .