Cap-Independent Translation: What's in a Name?

Eukaryotic translation initiation relies on the m⁷G cap present at the 5' end of all mRNAs. Some viral mRNAs employ alternative mechanisms of initiation based on internal ribosome entry. The 'IRES ideology' was adopted by researchers to explain the differential translation of cellular mRNAs when the cap recognition is suppressed. However, some cellular IRESs have already been challenged and others are awaiting their validation. As an alternative cap-independent mechanism, we propose adopting the concept of cap-independent translation enhancers (CITEs) for mammalian mRNAs. Unlike IRESs, CITEs can be located both within 5' and 3' UTRs and bind mRNA-recruiting translational components. The respective 5' UTRs are then inspected by the scanning machinery essentially in the same way as under cap-dependent translation.