Insights into the biology of IRES elements through riboproteomic approaches

Abstract

Translation initiation is a highly regulated process that exerts a strong influence on the posttranscriptional control of gene expression. Two alternative mechanisms govern translation initiation in eukaryotic mRNAs, the cap-dependent initiation mechanism operating in most mRNAs, and the internal ribosome entry site (IRES)-dependent mechanism, first discovered in picornaviruses. IRES elements are highly structured RNA sequences that, in most instances, require specific proteins for recruitment of the translation machinery. Some of these proteins are eukaryotic initiation factors. In addition, RNA-binding proteins (RBPs) play a key role in internal initiation control. RBPs are pivotal regulators of gene expression in response to numerous stresses, including virus infection. This review discusses recent advances on riboproteomic approaches to identify IRES transacting factors (ITAFs) and the relationship between RNA-protein interaction and IRES activity, highlighting the most relevant features on picornavirus and hepatitis C virus IRESs.

Figure 1

(a) Schematic representation of the picornavirus genome, using as example the foot-and-mouth disease viral RNA. (b) Schematic representation of the hepatitis C virus genome. The IRESs are depicted in blue, with indication of the domains referred to in the text. The position of the functional initiator AUGs, as well as the preferential binding sites of eIFs and ITAFs are indicated. Stable stem-loops located at the 5′ and 3′ end of the viral RNA are depicted in grey.