Ins and outs of IRES elements: function and significance

RNA and proteins are key components of all organisms. Internal ribosome entry site (IRES) elements are a diverse type of RNA regulatory structural elements that mediate end-independent, internal translation initiation in viral mRNAs and certain cellular mRNAs translated under stress conditions. Notably, viral IRES elements regulate translation initiation via a dynamic, modular RNA structure organization, which serves as the anchoring site for the ribosome guided by RNA-RNA and/or RNA-protein interactions. The implementation of advanced transcriptomics, proteomics, and computational methodologies has facilitated the identification of novel RNAs potentially translated using cap-independent mechanisms, harboring RNA structural elements with distinctive features. Here, we present a summary of the current understanding of IRES elements, focusing on the molecular functions and the RNA-binding proteins regulating IRES activity.