In most cases, translational control mechanisms result from the interaction of RNA-binding proteins with 5′- or 3′-untranslated regions (UTRs) of mRNA. In organisms ranging from viruses to humans, protein-mediated interactions between transcript termini result in the formation of an RNA loop. Such RNA ‘circularization' is thought to increase translational efficiency and, in addition, permits regulation by novel mechanisms, particularly 3′-UTR-mediated translational control. Two general mechanisms of translational inhibition by 3′-UTR-binding proteins have been proposed, one in which mRNA closure is disrupted and another in which mRNA closure is required. Experimental evidence for the latter is provided by studies of interferon-γ-mediated translational silencing of ceruloplasmin expression in monocytic cells. A multi-species analysis has shown that, in most vertebrates, 3′-UTRs are substantially longer than their 5′ counterparts, indicating a significant potential for regulation. In addition, the average length of 3′-UTR sequences has increased during evolution, suggesting that their utilization might contribute to organism complexity.